Science.gov

Sample records for protein-3 luteinizing hormone

  1. LH (Luteinizing Hormone) Test

    MedlinePlus

    ... for luteinizing hormone (LH), a hormone associated with reproduction and the stimulation of the release of an ... LH and FSH with the development of secondary sexual characteristics at an unusually young age are an ...

  2. Luteinizing hormone (LH) blood test

    MedlinePlus

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... to temporarily stop medicines that may affect the test results. Be sure to tell your provider about ...

  3. 21 CFR 862.1485 - Luteinizing hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Luteinizing hormone test system. 862.1485 Section... Systems § 862.1485 Luteinizing hormone test system. (a) Identification. A luteinizing hormone test system is a device intended to measure luteinizing hormone in serum and urine. Luteinizing...

  4. 21 CFR 862.1485 - Luteinizing hormone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Luteinizing hormone test system. 862.1485 Section... Systems § 862.1485 Luteinizing hormone test system. (a) Identification. A luteinizing hormone test system is a device intended to measure luteinizing hormone in serum and urine. Luteinizing...

  5. Marihuana smoking suppresses luteinizing hormone in women.

    PubMed

    Mendelson, J H; Mello, N K; Ellingboe, J; Skupny, A S; Lex, B W; Griffin, M

    1986-06-01

    Smoking a single 1-g marihuana cigarette containing 1.8% delta 9-tetrahydrocannabinol induced a 30% suppression of plasma luteinizing hormone levels (P less than .02) in women during the luteal phase of the menstrual cycle. After marihuana placebo cigarette smoking, no luteinizing hormone suppression was observed in the same women under double-blind conditions. Marihuana may have adverse effects upon reproductive function during the luteal phase of the menstrual cycle as a consequence of gonadotropin inhibition.

  6. 21 CFR 522.1820 - Pituitary luteinizing hormone for injection.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Pituitary luteinizing hormone for injection. 522... ANIMAL DRUGS § 522.1820 Pituitary luteinizing hormone for injection. (a) Specifications. The drug is a... standard pituitary luteinizing hormone and is reconstituted for use by addition of 5 milliliters of...

  7. 21 CFR 522.1820 - Pituitary luteinizing hormone for injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Pituitary luteinizing hormone for injection. 522... ANIMAL DRUGS § 522.1820 Pituitary luteinizing hormone for injection. (a) Specifications. The drug is a... standard pituitary luteinizing hormone and is reconstituted for use by addition of 5 milliliters of...

  8. 21 CFR 522.1820 - Pituitary luteinizing hormone for injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Pituitary luteinizing hormone for injection. 522... ANIMAL DRUGS § 522.1820 Pituitary luteinizing hormone for injection. (a) Specifications. The drug is a... standard pituitary luteinizing hormone and is reconstituted for use by addition of 5 milliliters of...

  9. 21 CFR 522.1820 - Pituitary luteinizing hormone for injection.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Pituitary luteinizing hormone for injection. 522... ANIMAL DRUGS § 522.1820 Pituitary luteinizing hormone for injection. (a) Specifications. The drug is a... standard pituitary luteinizing hormone and is reconstituted for use by addition of 5 milliliters of...

  10. Action of luteinizing hormone-releasing hormone: involvement of novel arachidonic acid metabolites.

    PubMed Central

    Snyder, G D; Capdevila, J; Chacos, N; Manna, S; Falck, J R

    1983-01-01

    Anterior pituitary cells were incubated in the presence of luteinizing hormone-releasing hormone and one of three inhibitors of arachidonic acid metabolism:indomethacin, an inhibitor of the cyclooxygenase system; nordihydroguaiaretic acid, an antioxidant that inhibits lipoxygenase; and icosatetraynoic acid, an acetylenic analogue of arachidonic acid that blocks all known pathways of arachidonic acid metabolism. Indomethacin was ineffective in blocking luteinizing hormone-releasing hormone-stimulated luteinizing hormone secretion. Nordihydroguaiaretic acid was only marginally capable of inhibiting luteinizing hormone-releasing hormone-stimulated luteinizing hormone secretion. Icosatetraynoic acid at 10 microM completely inhibited stimulated luteinizing hormone secretion. Addition of several epoxygenated arachidonic acid metabolites to cells in vitro resulted in secretion of luteinizing hormone equal to or greater than that induced by 10 nM luteinizing hormone-releasing hormone. The half-maximal effective dose for these compounds was approximately 50 nM. The 5,6-epoxyicosatrienoic acid was the most potent of the compounds tested. These studies suggest that luteinizing hormone-releasing hormone-stimulated luteinizing hormone release is closely coupled with the production of oxidized arachidonic acid metabolites. Moreover, one or more of the epoxygenated arachidonic acid metabolites might be a component of the cascade of reactions initiated by luteinizing hormone-releasing hormone that ultimately results in secretion of luteinizing hormone. PMID:6344087

  11. Dose-Response relationship of luteinizing hormone to luteinizing hormone—releasing hormone in man

    PubMed Central

    Kastin, Abba J.; Schally, Andrew V.; Gual, Carlos; Midgley, A. Rees; Miller, M. Clinton; Cabeza, Angela

    1971-01-01

    In previous clinical studies with highly purified porcine luteinizing hormone-releasing hormone (LH-RH), administration of the somewhat arbitrarily chosen doses of 700-1500 μg resulted in increased serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The present study determined the minimum effective dose as well as the relationship of the response of serum LH and FSH to the dose of LH-RH administered. Three normal men received i.v. injections of 1.1-810 μg of LH-RH. A dose of 10 μg of LH-RH caused a statistically significant elevation in serum LH. 30 μg of LH-RH significantly increased serum FSH levels. A highly significant linear trend was observed in the log dose-response curve. The results indicate that both LH and FSH release occurs in man with doses of LH-RH much lower than previously used and that a linear log dose-response relationship can be obtained. PMID:4932985

  12. 21 CFR 522.1820 - Pituitary luteinizing hormone powder for injection.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Pituitary luteinizing hormone powder for injection... ANIMAL DRUGS § 522.1820 Pituitary luteinizing hormone powder for injection. (a) Specifications. The drug... milligrams of standard pituitary luteinizing hormone and is reconstituted for use by addition of...

  13. 21 CFR 862.1485 - Luteinizing hormone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Luteinizing hormone test system. 862.1485 Section 862.1485 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

  14. 21 CFR 862.1485 - Luteinizing hormone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Luteinizing hormone test system. 862.1485 Section 862.1485 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

  15. 21 CFR 862.1485 - Luteinizing hormone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Luteinizing hormone test system. 862.1485 Section 862.1485 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

  16. Luteinizing hormone-releasing hormone agonists in premenopausal hormone receptor-positive breast cancer.

    PubMed

    Tan, Sing-Huang; Wolff, Antonio C

    2007-02-01

    Ovarian function suppression for the treatment of premenopausal breast cancer was first used in the late 19th century. Traditionally, ovarian function suppression had been accomplished irreversibly via irradiation or surgery, but analogues of the luteinizing hormone-releasing hormone (LH-RH) have emerged as reliable and reversible agents for this purpose, especially the LH-RH agonists. Luteinizing hormone-releasing hormone antagonists are in earlier stages of development in breast cancer and are not currently in clinical use. Luteinizing hormonereleasing hormone agonists act by pituitary desensitization and receptor downregulation, thereby suppressing gonadotrophin release. Limited information is available comparing the efficacies of the depot preparations of various agonists, but pharmacodynamic studies have shown comparable suppressive capabilities on estradiol and luteinizing hormone. At present, only monthly goserelin is Food and Drug Administration-approved for the treatment of estrogen receptor-positive, premenopausal metastatic breast cancer in the United States. Luteinizing hormone-releasing hormone agonists have proven to be as effective as surgical oophorectomy in premenopausal advanced breast cancer. They offer similar outcomes compared with tamoxifen, but the endocrine combination appears to be more effective than LH-RH agonists alone. In the adjuvant setting, LH-RH agonists versus no therapy reduce the annual odds of recurrence and death in women aged>50 years with estrogen receptor-positive tumors. Luteinizing hormone-releasing hormone agonists alone or in combination with tamoxifen have shown disease-free survival rates similar to chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil). Outcomes of chemotherapy with or without LH-RH agonists are comparable, though a few trials favor the combination in young premenopausal women (aged<40 years). Adjuvant LH-RH agonists with or without tamoxifen might be as efficacious as tamoxifen alone

  17. Luteinizing hormone release and androgen production of avian hybrids in response to luteinizing hormone releasing hormone injection.

    PubMed

    Mathis, G F; Burke, W H; McDougald, L R

    1983-04-01

    The levels of luteinizing hormone (LH) and androgens were measured in sterile avian hybrids. Guinea fowl-chicken and peafowl-guinea fowl hybrids were bled before and after injection with LH- releasing hormone (LHRH). The preinjection LH levels for the guinea fowl-chicken hybrids were below or at the very lower limit of the assay sensitivity and the peafowl-guinea fowl hybrids averaged 1.3 ng/ml. Within 10 min after LHRH injection, LH had increased dramatically in both hybrids and then began to slowly decline. Androgen levels in the guinea fowl-chicken hybrids increased from 16.2 pg/ml to 95.2 pg/ml and continued to increase, reaching 287 pg/ml at the last bleeding 60 min after injection.

  18. Hormonal Responses to Synthetic Luteinizing Hormone and Follicle Stimulating Hormone-Releasing Hormone in Man

    PubMed Central

    Besser, G. M.; McNeilly, A. S.; Anderson, D. C.; Marshall, J. C.; Harsoulis, P.; Hall, R.; Ormston, B. J.; Alexander, L.; Collins, W. P.

    1972-01-01

    The effects of the gonadotrophin-releasing hormone, synthetic decapeptide luteinizing hormone/follicle stimulating hormone-releasing hormone (LH/FSH-RH), have been studied in 18 normal men and five women in the follicular phase of their menstrual cycle. Rapid and dose-dependent (25 to 100 μg) increases in serum immunoreactive LH were seen, which reached a peak 20 to 30 minutes after a rapid intravenous injection. Similar but much smaller increases in serum immunoreactive FSH were seen. These conclusions have been validated by using two different immunoassay systems for each hormone. The LH/FSH-RH therefore causes both LH and FSH release in man as in animals but does not affect growth hormone, thyrotrophin, or ACTH. The gonadotrophin responses were the same in the women as in the men but were insufficient in the men to cause statistically significant changes in the serum levels of the gonadal steroid hormones, testosterone or oestradiol, or in their precursors 17 α-hydroxyprogesterone or progesterone. In the women, however, there was a rise in oestradiol after the 100-μg doses. The use of LH/FSH-RH will provide an important test to define the level of the lesion in hypogonadal patients and also should be valuable in the treatment of some types of male and female infertility. A simple and clinically useful LH/FSH-RH test of pituitary function is described (100 μg given intravenously), and the provisional normal responses of LH and FSH at 20 and 60 minutes are given. PMID:4339974

  19. Hypersecretion of luteinizing hormone and the polycystic ovary syndrome.

    PubMed

    Balen, A H

    1993-11-01

    Hypersecretion of luteinizing hormone (LH) is a significant cause of infertility and miscarriage in women with the polycystic ovary syndrome. Many theories have been suggested for the aetiology of pituitary oversecretion of LH. These include increased pulsatility of gonadotrophin releasing hormone (GnRH) hypothalamic dysfunction, altered pituitary sensitivity to GnRH, hyperinsulinaemic stimulation of the pituitary gland and perturbed ovarian-pituitary feedback of steroid hormones. None of these hypotheses fully explain the phenomenon of LH hypersecretion and there has been much debate in the literature on this subject. This paper reviews some of the important clinical studies that have examined the evolving story of hypersecretion of LH and presents in-vivo and in-vitro evidence that suggests that disordered ovarian-pituitary feedback is central to the problem, possibly through a perturbed secretion of nonsteroidal ovarian hormones.

  20. Suppression of androgen production by D-tryptophan-6-luteinizing hormone-releasing hormone in man.

    PubMed Central

    Tolis, G; Mehta, A; Comaru-Schally, A M; Schally, A V

    1981-01-01

    Four male transsexual subjects were given a superactive luteinizing hormone-releasing hormone (LHRH) analogue, D-tryptophan-6-LHRH at daily doses of 100 micrograms for 3--6 mo. A decrease in beard growth, acne, and erectile potency was noted; the latter was documented objectively with the recordings of nocturnal penile tumescence episodes. Plasma testosterone and dihydrotestosterone levels fell to castrate values; basal prolactin and luteinizing hormone levels showed a small decline, whereas the acutely releasable luteinizing hormone was significantly suppressed. A rise of plasma testosterone from castrate to normal levels was demonstrable with the use of human chorionic gonadotropin. Discontinuation of treatment led to a normalization of erectile potency and plasma testosterone. The suppression of Leydig cell function by D-tryptophan-6-LHRH might have wide application in reproductive biology and in endocrine-dependent neoplasia (where it could replace surgical castration). PMID:6456277

  1. Acute effects of marihuana on luteinizing hormone in menopausal women.

    PubMed

    Mendelson, J H; Cristofaro, P; Ellingboe, J; Benedikt, R; Mello, N K

    1985-11-01

    Plasma luteinizing hormone (LH) levels were determined under double blind crossover conditions in 10 healthy menopausal adult females prior to and following smoking of a 1-g marihuana cigarette containing 1.83% delta 9-tetrahydrocannabinol (THC) and a 1-g marihuana placebo cigarette. A significant increase in pulse rate and levels of intoxication occurred after marihuana smoking but not after smoking placebo cigarettes. LH levels determined before administration of marihuana and placebo cigarettes were not significantly different and were within the range of normal values for healthy menopausal women. No significant differences were found between LH levels following marihuana and placebo smoking.

  2. Future possibilities in the prevention of breast cancer: Luteinizing hormone-releasing hormone agonists

    PubMed Central

    Spicer, Darcy V; Pike, Malcolm C

    2000-01-01

    The cyclic production of estrogen and progesterone by the premenopausal ovary accounts for the steep rise in breast cancer risk in premenopausal women. These hormones are breast cell mitogens. By reducing exposure to these ovarian hormones, agonists of luteinizing hormone-releasing hormone (LHRH) given to suppress ovarian function may prove useful in cancer prevention. To prevent deleterious effects of hypoestrogenemia, the addition of low-dose hormone replacement to the LHRH agonist appears necessary. Pilot data with such an approach indicates it is feasible and reduces mammographic densities. PMID:11250719

  3. Luteinizing hormone acts at the hippocampus to dampen spatial memory.

    PubMed

    Burnham, Veronica; Sundby, Christopher; Laman-Maharg, Abigail; Thornton, Janice

    2017-03-01

    Luteinizing hormone (LH) rises dramatically during and after menopause, and has been correlated with an increased incidence of Alzheimer's disease and decreased memory performance in humans and animal models. To test whether LH acts directly on the dorsal hippocampus to affect memory, ovariectomized female rats were infused with either the LH-homologue human chorionic gonadotropin (hCG) or the LH receptor antagonist deglycosylated-hCG (dg-hCG). Infusion of hCG into either the lateral ventricle or the dorsal hippocampus caused significant memory impairments in ovariectomized estradiol-treated females. Consistent with this, infusion of the LH antagonist dg-hCG into the dorsal hippocampus caused an amelioration of memory deficits in ovariectomized females. Furthermore, the gonadotropin-releasing hormone antagonist Antide, failed to act in the hippocampus to affect memory. These findings demonstrate a significant role for LH action in the dorsal hippocampus in spatial memory dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

    Choi, Janet; Smitz, Johan

    2014-03-05

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

  5. Lutein

    MedlinePlus

    ... including age-related macular degeneration (AMD), cataracts, and retinitis pigmentosa. Some people also use it for preventing colon ... risk of respiratory infections An eye disease called retinitis pigmentosa. Some early evidence suggests that lutein might be ...

  6. Active immunization to luteinizing hormone releasing hormone to inhibit the induction of mammary tumors in the rat

    SciTech Connect

    Ravdin, P.M.; Jordan, V.C.

    1988-01-01

    Immunization of female rats with a bovine serum albumin-luteinizing hormone releasing hormone conjugate results in suppression of dimethylbenzanthracene mammary tumor incidence. Tumor incidence was 1.3, and 1.29 tumors per rat in bovine serum albumin alone (n = 10) and unimmunized (n = 18) control groups, but no tumors were found in the bovine serum albumin-luteinizing hormone releasing hormone conjugate immunized animals (n = 10). In a second experiment immunization with bovine serum albumin-luteinizing hormone releasing hormone conjugates reduced tumor incidence to 0.3 tumors per rat (n = 10) from the 1.2 tumors per animal seen in the control animals (n = 10) immunized with bovine serum albumin alone. Bovine serum albumin-luteinizing hormone immunization caused the production of anti-LHRH antibodies, an interruption of estrous cycles, lowered serum estradiol and progesterone levels, and atrophy of the ovaries and uteri. Immunization BSA-hormone conjugates is a novel anti-tumor strategy.

  7. A Nested Case-Control Study of Luteinizing Hormone Variants and Risk of Breast Cancer

    DTIC Science & Technology

    1999-10-01

    is dependent on the secretion of pituitary gonadotropins -- follicle stimulating hormone (FSH) and luteinizing hormone (H-I). Recently, an...advantage of an on-going prospective cohort study of hormones and breast cancer. Serum samples from cohort subjects are being assayed for...luteinizing hormone caused by two chorionic gonadotropin -type amino-acid substitutions. Biochem Biophysic Res Com. 1994; 200:584-90. 5. Sairam MR. Role

  8. Luteinizing Hormone-Releasing Hormone Distribution in the Anterior Hypothalamus of the Female Rats

    PubMed Central

    Castañeyra-Ruiz, Leandro; González-Marrero, Ibrahim; Castañeyra-Ruiz, Agustín; González-Toledo, Juan M.; Castañeyra-Ruiz, María; de Paz-Carmona, Héctor; Castañeyra-Perdomo, Agustín; Carmona-Calero, Emilia M.

    2013-01-01

    Luteinizing hormone-releasing hormone (LHRH) neurons and fibers are located in the anteroventral hypothalamus, specifically in the preoptic medial area and the organum vasculosum of the lamina terminalis. Most luteinizing hormone-releasing hormone neurons project to the median eminence where they are secreted in the pituitary portal system in order to control the release of gonadotropin. The aim of this study is to provide, using immunohistochemistry and female brain rats, a new description of the luteinizing hormone-releasing hormone fibers and neuron localization in the anterior hypothalamus. The greatest amount of the LHRH immunoreactive material was found in the organum vasculosum of the lamina terminalis that is located around the anterior region of the third ventricle. The intensity of the reaction of LHRH immunoreactive material decreases from cephalic to caudal localization; therefore, the greatest immunoreaction is in the organum vasculosum of the lamina terminalis, followed by the dorsomedial preoptic area, the ventromedial preoptic area, and finally the ventrolateral medial preoptic area, and in fibers surrounding the suprachiasmatic nucleus and subependymal layer on the floor of the third ventricle where the least amount immunoreactive material is found. PMID:25938107

  9. Leptin increases luteinizing hormone secretion of fasting female rats.

    PubMed

    Dagklis, T; Kouvelas, D; Kallaras, K; Papazisis, G; Petousis, S; Margioula-Siarkou, C; Skepastianos, P; Tarlatzis, B C

    2015-01-01

    To investigate whether leptin acts directly on the anterior hypophysis by influencing gonadotropin secretion in vivo. Cycling female rats were catheterised for frequent blood sampling and were either fasted or allowed free access to food. Stereotactic lesion of the medial preoptic area (MPOA) of the hypothalamus was performed in order to eliminate gonadotropin releasing hormone (GnRH) production. Leptin was administered at a dose of one mg/kg i.v. and blood samples were taken just before leptin administration and then after 30, 60, 90, 120, and 180 minutes. Plasma gonadotropin levels were determined. With completion of sampling, the brains were removed and the localisation of the lesions was verified histologically. Leptin at one mg/kg induced an increase in luteinizing hormone (LH) secretion in fasting rats, both in those with a lesion and those with intact medial preoptic area with a peak occurring 90 minutes after infusion. The augmenting effect was more prominent when the hypothalamus was intact. There was no effect in fed animals with or without lesion. Similarly, no effect was observed on follicle stimulating hormone (FSH) levels in any of the experimental groups. Leptin acts directly on the hypophysis enhancing LH but not FSH secretion. Nutritional state influences leptin's effect on the hypothalamus and the hypophysis.

  10. Role of luteinizing hormone in luteotropic complex of pregnant hamster

    SciTech Connect

    Tamura, H.; Greenwald, G.S.

    1987-04-01

    Hamsters were hypophysectomized on day 4 of pregnancy and injected subcutaneously on days 4-7 with various combinations of 200 ..mu..g prolactin (Prl), 10 ..mu..g follicle-stimulating hormone (FSH), and 20 ..mu..g luteinizing hormone (LH) in polyvinylpyrrolidone (PVP) to decrease its rate of absorption or in saline. End points for luteal function on day 8 were maintenance of pregnancy, serum progesterone (P/sub 4/), luteal weight, and luteal binding for human chorionic gonadotropin, FSH, and Prl. After hypophysectomy, a drastic decline occurred in all parameters including an 89% decrease in luteal weight. Injection of Prl did not maintain pregnancy nor serum P/sub 4/ but partially maintained luteal weight and human chorionic gonadotropin binding sites per corpus luteum. The minimal luteotropic complex of Prl and FSH was effective in maintaining pregnancy and significantly increased serum P/sub 4/ and Prl and FSH receptors but not to control levels. Thus, the luteotropic activity of LH was only demonstrable when it was injected in a long-acting form; when delivered as a bolus, LH (saline) was luteolytic. P/sub 4/ and estradiol were measured by radioimmunoassay. Radioiodinated gonadotropins were prepared. The percentage of tracer reacting with an excess of receptor were 51% of /sup 125/I-FSH and 45.9% of /sup 125/I-hCG using whole homogenates of hamster ovaries.

  11. Radioiodination of chicken luteinizing hormone without affecting receptor binding potency

    SciTech Connect

    Kikuchi, M.; Ishii, S. )

    1989-12-01

    By improving the currently used lactoperoxidase method, we were able to obtain radioiodinated chicken luteinizing hormone (LH) that shows high specific binding and low nonspecific binding to a crude plasma membrane fraction of testicular cells of the domestic fowl and the Japanese quail, and to the ovarian granulosa cells of the Japanese quail. The change we made from the original method consisted of (1) using chicken LH for radioiodination that was not only highly purified but also retained a high receptor binding potency; (2) controlling the level of incorporation of radioiodine into chicken LH molecules by employing a short reaction time and low temperature; and (3) fractionating radioiodinated chicken LH further by gel filtration using high-performance liquid chromatography. Specific radioactivity of the final {sup 125}I-labeled chicken LH preparation was 14 microCi/micrograms. When specific binding was 12-16%, nonspecific binding was as low as 2-4% in the gonadal receptors. {sup 125}I-Labeled chicken LH was displaced by chicken LH and ovine LH but not by chicken follicle-stimulating hormone. The equilibrium association constant of quail testicular receptor was 3.6 x 10(9) M-1. We concluded that chicken LH radioiodinated by the present method is useful for studies of avian LH receptors.

  12. Regional differences in the pituitary distribution of luteinizing hormone in the gonadectomized and proestrous female rat

    EPA Science Inventory

    Previous data have shown regional differences in the presence of anterior pituitary luteinizing hormone (LH) that generally correlate with comparable disparities in the distribution of gonadotropes throughout the gland. In female rats, the differences are apparent over the estro...

  13. Regional differences in the pituitary distribution of luteinizing hormone in the gonadectomized and proestrous female rat

    EPA Science Inventory

    Previous data have shown regional differences in the presence of anterior pituitary luteinizing hormone (LH) that generally correlate with comparable disparities in the distribution of gonadotropes throughout the gland. In female rats, the differences are apparent over the estro...

  14. Expression of luteinizing hormone receptors in the mouse penis.

    PubMed

    Kokk, Kersti; Kuuslahti, Marianne; Keisala, Tiina; Purmonen, Sami; Kaipia, Antti; Tammela, Teuvo; Orro, Helen; Simovart, Helle-Evi; Pöllänen, Pasi

    2011-01-01

    The role of luteinizing hormone (LH) in the regulation of normal reproductive functions in males and females is quite well established. Besides the expression of LH receptors in the target cells in gonads, it has been found in several extragonadal organs. There is no information about the expression of LH receptors in the penis up to now. The aim of the present study is to investigate the expression of the LH receptor in the mouse penis to see if LH effects are possible in the penis. BALB/c mice were used as donors of normal penis and testis tissue. Immunocytochemistry, Western blotting, and quantitative reverse transcriptase polymerase chain reactions (RT-PCRs) were used for the detection of the LH receptor. Positive immunoreaction for LH receptors was present in the nuclei of urethral epithelium and endothelial cells of cavernous spaces in the corpus cavernosum and corpus spongiosum penis. Western blotting experiments demonstrated the presence of LH antigen at M(r) = 97.4 and 78 kd. Quantitative RT-PCRs confirmed the expression of LH receptor in the penis. Our results show that LH receptor is expressed in the body of the mouse penis; thus, it may directly regulate functions of penile tissue.

  15. Localization of luteinizing hormone receptor protein in the human ovary.

    PubMed

    Yung, Y; Aviel-Ronen, S; Maman, E; Rubinstein, N; Avivi, C; Orvieto, R; Hourvitz, A

    2014-09-01

    The luteinizing hormone receptor (LHR) plays a pivotal role during follicular development. Consequently, its expression pattern is of major importance for research and has clinical implications. Despite the accumulated information regarding LHR expression patterns, our understanding of its expression in the human ovary, specifically at the protein level, is incomplete. Therefore, our aim was to determine the LHR protein localization and expression pattern in the human ovary. We examined the presence of LHR by immunohistochemical staining of human ovaries and western blots of mural granulosa and cumulus cells aspirated during IVF treatments. We were not able to detect LHR protein staining in primordial or primary follicles. We observed equivocal positive staining in granulosa cells and theca cells of secondary follicles. The first appearance of a clear signal of LHR protein was observed in granulosa cells and theca cells of small antral follicles, and there was evidence of increasing LHR production as the follicles mature to the pre-ovulatory stage. After ovulation, LHR protein was ubiquitously produced in the corpus luteum. To confirm the expression pattern in granulosa cells and cumulus cells, we performed western blots and found that LHR expression was stronger in granulosa cells than in cumulus cells, with the later demonstrating low, but still significant, amounts of LHR protein. In summary, we conclude that LHR protein starts to appear on granulosa cells and theca cells of early antral follicles, and low but significant expression of LHR exists also in the cumulus cells. These results may have implications for the future design of clinical protocols and culture mediums for in vitro fertilization and especially in vitro maturation of oocytes.

  16. Precocious puberty associated with neurofibromatosis and optic gliomas. Treatment with luteinizing hormone releasing hormone analogue.

    PubMed

    Laue, L; Comite, F; Hench, K; Loriaux, D L; Cutler, G B; Pescovitz, O H

    1985-11-01

    Seven children with central precocious puberty and either neurofibromatosis and/or optic gliomas were referred to the National Institutes of Health, Bethesda, Md, for evaluation and treatment with the long-acting luteinizing hormone releasing hormone analogue (LHRHa) D-Trp6-Pro9-NEt-LHRH. Only six of the seven children chose to receive treatment. Four children presented with neurofibromatosis, three of whom also had optic gliomas; the remaining three children had isolated optic gliomas, without other neurocutaneous stigmas. All had central precocious puberty mediated by activation of the hypothalamic-pituitary-gonadal axis. Six months of LHRHa therapy caused suppression of gonadotropin and sex steroid levels, stabilization or regression of secondary sexual characteristics, and decreases in growth velocity and the rate of bone age maturation. We conclude that LHRHa therapy is effective in the treatment of central precocious puberty secondary to neurofibromatosis and/or optic gliomas.

  17. Migration of luteinizing hormone-releasing hormone (LHRH) neurons in early human embryos.

    PubMed

    Schwanzel-Fukuda, M; Crossin, K L; Pfaff, D W; Bouloux, P M; Hardelin, J P; Petit, C

    1996-03-11

    Luteinizing hormone-releasing hormone (LHRH) neurons originate in the epithelium of the medial olfactory pit and migrate from the nose into the forebrain along nerve fibers rich in neural cell adhesion molecule (N-CAM). The present study examined the ontogenesis of LHRH neurons in early human embryos and found a similar pattern of development of these cells. Luteinizing hormone-releasing hormone immunoreactivity was detected in the epithelium of the medial olfactory pit and in cells associated with the terminal-vomeronasal nerves at 42 (but not 28-32) days of gestation. The migration route of these cells was examined with antibodies to N-CAM and antibodies to polysialic acid (PSA-N-CAM), which is present on N-CAM at certain stages of development. Neural cell adhesion molecule immunoreactivity was present in a population of cells in the olfactory placode of the earliest embryos examined (28-32 days) and later (42 and 46 days) throughout the migration route. The PSA-N-CAM immunoreactivity was not detected until 42 days and was present in a more limited distribution in nerve fibers streaming from the olfactory placode and along the caudal part of the migration route below the forebrain. Previous studies have indicated that the highly sialated form of N-CAM is less adhesive. The PSA-N-CAM may therefore facilitate the migration of these cells by lessening the adhesion between the fascicles that make up the migration route, expediting the passage of cords of LHRH cells between the nerve fibers as these cells move toward the brain.

  18. The role of testicular hormones and luteinizing hormone in spatial memory in adult male rats.

    PubMed

    McConnell, Sarah E A; Alla, Juliet; Wheat, Elizabeth; Romeo, Russell D; McEwen, Bruce; Thornton, Janice E

    2012-04-01

    Attempts to determine the influence of testicular hormones on learning and memory in males have yielded contradictory results. The present studies examined whether testicular hormones are important for maximal levels of spatial memory in young adult male rats. To minimize any effect of stress, we used the Object Location Task which is a spatial working memory task that does not involve food or water deprivation or aversive stimuli for motivation. In Experiment 1 sham gonadectomized male rats demonstrated robust spatial memory, but gonadectomized males showed diminished spatial memory. In Experiment 2 subcutaneous testosterone (T) capsules restored spatial memory performance in gonadectomized male rats, while rats with blank capsules demonstrated compromised spatial memory. In Experiment 3, gonadectomized male rats implanted with blank capsules again showed compromised spatial memory, while those with T, dihydrotestosterone (DHT), or estradiol (E) capsules demonstrated robust spatial memory, indicating that T's effects may be mediated by its conversion to E or to DHT. Gonadectomized male rats injected with Antide, a gonadotropin-releasing hormone receptor antagonist which lowers luteinizing hormone levels, also demonstrated spatial memory, comparable to that shown by T-, E-, or DHT-treated males. These data indicate that testicular androgens are important for maximal levels of spatial working memory in male rats, that testosterone may be converted to E and/or DHT to exert its effects, and that some of the effects of these steroid hormones may occur via negative feedback effects on LH.

  19. In vivo pharmacological evaluation of a lactose-conjugated luteinizing hormone releasing hormone analogue.

    PubMed

    Moradi, Shayli Varasteh; Varamini, Pegah; Steyn, Frederik; Toth, Istvan

    2015-11-10

    In the current study, the efficacy and pharmacokinetic profile of lactose-conjugated luteinizing hormone releasing hormone (LHRH) was examined following oral administration in male rats. A rapid and sensitive liquid chromatography/mass spectrometry technique was developed and applied for measuring the concentration of lactose[Q(1)][w(6)]LHRH (compound 1) in rat plasma in order to allow measurement of pharmacokinetic parameters. LH release was evaluated using a sandwich ELISA. Maximum serum concentration (Cmax = 0.11 μg/ml) was reached at 2h (Tmax) following oral administration of the compound at 10mg/kg. The half-life was determined to be 2.6h. The absolute bioavailability of the orally administered compound was found to be 14%, which was a remarkable improvement compared to zero-to-low oral bioavailability of the native peptide. Compound 1 was effective in stimulating LH release at 20mg/kg after oral administration. The method was validated at a linear range of 0.01-20.0 μg/ml and a correlation coefficient of r(2) ≥ 0.999. The accuracy and precision values showed the reliability and reproducibility of the method for evaluation of the pharmacokinetic parameters. These findings showed that the lactose derivative of LHRH has a therapeutic potential to be further developed as an orally active therapeutics for the treatment of hormone-dependent diseases.

  20. Concentrations of triiodothyronine, growth hormone, and luteinizing hormone in the plasma of thyroidectomised fowl (Gallus domesticus).

    PubMed

    Harvey, S; Sterling, R J; Klandorf, H

    1983-05-01

    Surgical thyroidectomy increased (P less than 0.05) the basal concentrations of growth hormone (GH) and luteinizing hormone (LH) in the plasma of 10- to 12-week-old domestic fowl. The administration of thyrotrophin releasing hormone (TRH) (100 micrograms, sc) increased (P less than 0.01) the GH concentration in both intact and thyroidectomised birds. The magnitude of the TRH-induced increase in GH level was greater (P less than 0.01) in thyroidectomised birds than in intact controls. Although TRH had no effect on LH secretion in the controls, it induced a small (P less than 0.05) rise in the plasma LH level in thyroidectomised birds. In both the intact and thyroidectomised birds the LH concentration was enhanced (P less than 0.05) following the administration of LH-releasing hormone (LH-RH) (20 micrograms, sc). The increase in the LH level by LH-RH in the thyroidectomised birds was greater (P less than 0.001) than that in the intact controls. Plasma GH concentrations were unaffected by LH-RH treatment. These results suggest that thyroid hormones inhibit the secretion of LH and GH in birds. In thyroidectomised birds low levels of immunoreactive triiodothyronine (T3)-like material were measurable in the circulation, despite the absence of regenerated thyroid tissue. The administration of TRH (100 micrograms, sc) did not enhance the plasma level of this material in thyroidectomised birds, whereas plasma T3 concentrations were enhanced in intact birds following TRH treatment. These results suggest that the T3 immunoreactive substance in thyroidectomised birds is extrathyroidal in origin.

  1. Luteinizing hormone secretion as influenced by age and estradiol in the prepubertal gilt

    USDA-ARS?s Scientific Manuscript database

    The aim of this study was to determine if there is an age related reduction in the sensitivity of the negative feedback action of estradiol on luteinizing hormone (LH) secretion in the prepubertal gilt. Ovariectomized gilts at 90 (n = 12), 150 (n = 11) or 210 (n = 12) days of age received estradiol ...

  2. PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS

    EPA Science Inventory

    PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS
    Bielmeier1, S.R., D.S. Best2, and M.G. Narotsky2; 1University of North Carolina at Chapel Hill, Curriculum in Toxicology, 2Reproductive Toxicology Division, U.S. Enviro...

  3. PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS

    EPA Science Inventory

    PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS
    Bielmeier1, S.R., D.S. Best2, and M.G. Narotsky2; 1University of North Carolina at Chapel Hill, Curriculum in Toxicology, 2Reproductive Toxicology Division, U.S. Enviro...

  4. Long-term suppression of ovarian function by a luteinizing-hormone releasing hormone agonist implant in patients with endometriosis.

    PubMed

    Fraser, H M; Sandow, J; Cowen, G M; Lumsden, M A; Haining, R; Smith, S K

    1990-01-01

    Ten endometriosis patients received luteinizing hormone releasing hormone (LH-RH) agonist (buserelin) implant injections (6.6 mg subcutaneously) at days 0, 42, 84 and 126. Serum LH and follicle-stimulating hormone (FSH) were lowered by day 14. Luteinizing hormone remained at basal concentrations while FSH returned to values in the low-normal range of the menstrual cycle by day 35. At the end of the luteal phase during which treatment commenced, estrone and pregnanediol declined and remained at postmenopausal or early follicular phase values until days 305 to 460. Time to first ovulation ranged from 321 to 481 days after starting treatment. After the initial menstruation, only three instances of bleeding occurred during treatment. Pelvic pain was relieved or markedly reduced by day 42 and remained absent throughout the period of ovarian suppression. These results indicate the potential of a long-acting LH-RH agonist implant to form the basis for the treatment of symptomatic endometriosis.

  5. Annual cycle of plasma luteinizing hormone and sex hormones in male and female mallards (Anas platyrhynchos)

    USGS Publications Warehouse

    Donham, R.S.

    1979-01-01

    Comparisons between 'wild'and 'game farm' mallards (Anas platyrhynchos) were made to assess the differences in the temporal changes of plasma hormones. Seasonal variation in the levels of immunoreactive luteinizing hormone (LH), testosterone, 5 -dihydrotestosterone (DHT), estrone, estradiol-17i?? and progesterone were measured in male and female mallards. In all birds there was a vernal increase in the concentrations of LH and testosterone in plasma which were correlated with the development of the testes and ovaries prior to and during the nesting season. The concentrations of estrogens in the plasma of the females were, in general, slightly higher during the nesting season but were much lower than the levels of testosterone. The highest levels of LH and testosterone in the females coincided precisely with the period of egg laying which occurred approximately one month earlier in game farm females than in wild females. The concentrations of LH and testosterone in the plasma of females decreased rapidly during incubation. In wild males, the decline in levels of these hormones temporally coincided with that of females. In contrast, plasma levels of LH and testosterone of males of the game farm stock remained elevated after the beginning of incubation in females to which they were paired. On the basis of these results and an examination of the literature, it appears that domestication results in: 1) increased reproductive potential through earlier initiation of nesting and by delay of the termination of reproduction until later in the summer; and 2) a decrease in the synchronization of the hormonal events supporting reproduction between the male and female of a pair. Testicular weights and plasma levels of testosterone become higher in game farm and domestic males than in the wild stock but levels of LH are similar.

  6. Luteinizing Hormone-Releasing Hormone Enhances T Cell Recovery following Allogeneic Bone Marrow Transplantation1

    PubMed Central

    Goldberg, Gabrielle L.; King, Christopher G.; Nejat, Rebecca A.; Suh, David Y.; Smith, Odette M.; Bretz, Jamison C.; Samstein, Robert M.; Dudakov, Jarrod A.; Chidgey, Ann P.; Chen-Kiang, Selina; Boyd, Richard L.; van den Brink, Marcel R. M.

    2009-01-01

    Posttransplant immunodeficiency, specifically a lack of T cell reconstitution, is a major complication of allogeneic bone marrow transplantation. This immunosuppression results in an increase in morbidity and mortality from infections and very likely contributes to relapse. In this study, we demonstrate that sex steroid ablation using leuprolide acetate, a luteinizing hormone-releasing hormone agonist (LHRHa), increases the number of lymphoid and myeloid progenitor cells in the bone marrow and developing thymocytes in the thymus. Although few differences are observed in the peripheral myeloid compartments, the enhanced thymic reconstitution following LHRHa treatment and allogeneic bone marrow transplantation leads to enhanced peripheral T cell recovery, predominantly in the naive T cell compartment. This results in an increase in T cell function in vivo and in vitro. Graft-versus-host-disease is not exacerbated by LHRHa treatment and graft-versus-tumor activity is maintained. Because LHRHa allows for reversible (and temporary) sex steroid ablation, has a strong safety profile, and has been clinically approved for diseases such as prostate and breast cancer, this drug treatment represents a novel therapeutic approach to reversal of thymic atrophy and enhancement of immunity following immunosuppression. PMID:19380833

  7. Rationally designed cyclic analogues of luteinizing hormone-releasing hormone: enhanced enzymatic stability and biological properties.

    PubMed

    Laimou, Despina; Katsila, Theodora; Matsoukas, John; Schally, Andrew; Gkountelias, Kostas; Liapakis, George; Tamvakopoulos, Constantin; Tselios, Theodore

    2012-12-01

    This article describes the rational design, synthesis and pharmacological properties of amide-linked cyclic analogues of Luteinizing Hormone-Releasing Hormone (LHRH) with substitutions at positions 1 (Pro), 6 (D-Leu/D-Trp), 9 (Aze) and 10 (BABA/Acp). These LHRH analogues fulfil the conformational requirements that are known in the literature (bend in the 5-8 segment) to be essential for receptor recognition and activation. Although, they are characterised by an overall low binding affinity to the LHRH-I receptor, the cyclic analogues that were studied and especially the cyclo(1-10)[Pro(1), D-Leu(6), BABA(10)] LHRH, exhibit a profoundly enhanced in vitro and in vivo stability and improved pharmacokinetics in comparison with their linear counterpart and leuprolide. Upon receptor binding, cyclo(1-10)[Pro(1), D-Leu(6), BABA(10)] LHRH causes testosterone release in C57/B16 mice (in vivo efficacy) that is comparable to that of leuprolide. Testosterone release is an acutely dose dependent effect that is blocked by the LHRH-I receptor antagonist, cetrorelix. The pharmacokinetic advantages and efficacy of cyclo(1-10)[Pro(1), D-Leu(6), BABA(10)] LHRH render this analogue a promising platform for future rational drug design studies towards the development of non-peptide LHRH mimetics.

  8. Luteinizing hormone--releasing hormone agonists: a quick reference for prevalence rates of potential adverse effects.

    PubMed

    Walker, Lauren M; Tran, Susan; Robinson, John W

    2013-12-01

    Men with prostate cancer (PCa) frequently undergo androgen deprivation therapy (ADT), typically in the form of a depot injection of luteinizing hormone-releasing hormone agonists (LHRHa). LHRHa are associated with many adverse effects (eg, hot flashes, sexual dysfunction, loss of muscle mass, osteopenia, metabolic syndrome), which drastically impact patient quality of life. This literature review, which includes a comprehensive table documenting prevalence rates, provides a quick reference for health care professionals involved in the care of men undergoing ADT with LHRHa. Primary sources were acquired from PubMed using the search terms "androgen deprivation therapy" and each potentially adverse effect (eg, "androgen deprivation therapy and hot flashes"). Commonly cited review articles were also examined for citations of original studies containing prevalence rates. More than 270 articles were reviewed. In contrast to many existing reviews, rates are cited exclusively from original sources. The prevalence rates, obtained from original sources, suggest that more than half of documented adverse effects are experienced by as many as 40% or more of patients. A critique of the literature is also provided. Although there is a vast literature of both original and review articles on specific adverse effects of LHRHa, the quality of research on prevalence rates for some adverse effects is subpar. Many review articles contain inaccuracies and do not cite original sources. The table of prevalence rates will serve as a quick reference for health care providers when counseling patients and will aid in the development of evidence-based patient education materials.

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

    PubMed

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

    2015-01-01

    This paper presents the results of an experimental study of the biosynthesis of magnetite nanoparticles (BMNPs) with particle sizes between 10 nm and 60 nm. The biocompatible magnetic nanoparticles are produced from Magnetospirillum magneticum (M.M.) bacteria that respond to magnetic fields. M.M. bacteria were cultured and used to synthesize magnetite nanoparticles. This was done in an enriched magnetic spirillum growth medium (EMSGM) at different pH levels. The nanoparticle concentrations were characterized with UV-Visible (UV-Vis) spectroscopy, while the particle shapes were elucidated via transmission electron microscopy (TEM). The structure of the particles was studied using X-ray diffraction (XRD), while the hydrodynamic radii, particle size distributions and polydispersity of the nanoparticles were characterized using dynamic light scattering (DLS). Carbodiimide reduction was also used to functionalize the BMNPs with a molecular recognition unit (luteinizing hormone releasing hormone, LHRH) that attaches specifically to receptors that are over-expressed on the surfaces of most breast cancer cell types. The resulting nanoparticles were examined using Fourier Transform Infrared (FTIR) spectroscopy and quantitative image analysis. The implications of the results are then discussed for the potential development of magnetic nanoparticles for the specific targeting and treatment of breast cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Establishment and clinical application of enzyme immunoassays for determination of luteinizing hormone releasing hormone and metastin.

    PubMed

    Katagiri, Fumihiko; Tomita, Kenji; Oishi, Shinya; Takeyama, Masaharu; Fujii, Nobutaka

    2007-06-01

    Metastin, a 54-residue peptide, was identified as the cognate ligand of human G-protein-coupled receptor GPR54. Since metastin is a gene product of the human metastasis suppressor gene 'KiSS-1', early studies on metastin were focused on its activity as a tumor metastasis suppressor. Recently, there have been some reports that metastin is found in human plasma and is particularly abundant in the plasma of pregnant women. Dysfunction of the GPR54 receptor causes diseases that are characterized by an insufficient release of gonadotropin and lack or delay of pubertal maturation. This information strongly suggests that metastin is involved in the regulation of reproductive endocrine functions. In order to determine the plasma levels of metastin and luteinizing hormone releasing hormone (LHRH) in an isolated hypogonadotropic hypogonadism (IHH) patient, who received intermittent administrations of LHRH, we tried to establish a sensitive and specific enzyme immunoassay. The plasma LHRH levels of the patient were very high, while plasma metastin levels were at almost the same levels as circadian rhythms of healthy male humans. In the central nervous system, metastin stimulates the neuroendocrine reproductive axis. However, the effects of peripheral metastin are not known. Our result suggested that peripheral metastin had a genesis and activity different from central metastin.

  11. Regulation of rat luteinizing hormone subunit messenger ribonucleic acids by gonadal steroid hormones.

    PubMed Central

    Gharib, S D; Bowers, S M; Need, L R; Chin, W W

    1986-01-01

    Little is known about the hormonal regulation of luteinizing hormone (LH) biosynthesis. We have studied the regulation of LH messenger RNA (mRNA) levels by gonadal-steroid hormones in the rat. In one set of experiments, male and female rats were surgically gonadectomized (GDX) and killed 1, 3, 7, 14, 22, and 31 d postoperatively. In another set of experiments, male and female rats were surgically GDX and were injected subcutaneously with testosterone propionate (500 micrograms/100 g body wt per d) or 17 beta-estradiol 3-benzoate (10 micrograms/100 g body wt per d), respectively, beginning 3 wk postoperatively. Levels of serum LH were determined by radioimmunoassay and levels of LH subunit mRNAs in single pituitary glands were determined by blot hybridization analysis using labeled synthetic oligodeoxyribonucleotide probes that correspond to portions of the coding regions of the rat alpha- and LH beta-subunit mRNAs. 4 wk after gonadectomy, serum LH levels rose nine- and 20-fold, while alpha-subunit mRNA levels rose six- and 10-fold, and LH beta-subunit levels rose seven- and 14-fold, compared with controls in males and females, respectively. In gonadal-steroid hormone-treated male and female GDX rats, serum LH levels fell to 8 and 36% of control values, while alpha-subunit mRNA levels declined to 22 and 19%, and LH beta-subunit mRNA levels declined to 6 and 10% of control values, 48 h after injections were initiated, in males and females, respectively. We conclude that gonadal-steroid hormones negatively regulate the levels of both subunit mRNAs in GDX rats in a pattern that parallels the changes in serum LH values. These data suggest that gonadal-steroid hormone regulation of LH biosynthesis occurs, at least in part, at the level of LH subunit mRNAs due to effects at the transcriptional and/or RNA stability levels. Images PMID:2418065

  12. Hypothalamic hypopituitarism in a patient with a basal encephalocoele--treatment with luteinizing hormone-releasing hormone.

    PubMed Central

    Morris, D. V.; Mason, W. P.; Wilson-Holt, N.; Adams, J.; Keene, M.; Tanner, J.; Jacobs, H. S.

    1984-01-01

    A 20-year-old patient presented with primary amenorrhoea and growth hormone deficiency caused by a basal encephalocoele. She was found to have developed diabetes insipidus in the 8 years following diagnosis. Gonadotrophin release in response to bolus injection of luteinizing hormone-releasing hormone (LHRH) was normal, as was thyrotrophin and adrenocorticotrophin (ACTH) secretion. Pulsatile administration of LHRH by the subcutaneous route resulted in normal ovulation and subsequent menstruation. The investigation and management of patients with basal encephalocoeles are discussed in the light of these findings. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:6384984

  13. Response of the corpus luteum to luteinizing hormone.

    PubMed Central

    Niswender, G D

    1981-01-01

    The response of steroidogenic tissues to tropic hormones is regulated in part by specific receptors in the target cells for the stimulatory hormone. As a result of hormone binding to receptor the enzyme adenylate cyclase is activated with a resultant increase in intracellular levels of cAMP. Enhanced protein kinase activity then leads to increased steroidogenesis via several possible mechanisms, including direct activation of components of steroidogenic enzyme systems via phosphorylation. The initial effects of tropic hormones such as LH are dependent upon the number of receptors present on the surface of the target cell. Numerous factors influence the number of LH receptors in the corpus luteum. A model is presented for the mechanisms involved in the loss and renewal of LH receptors in the luteal cell. The life of the LH receptor on luteal cells appears to be a single binding of hormone. The hormone-receptor complex is then internalized by endocytosis and the hormone is degraded in lysosomes. After internalization the receptor is also degraded in lysosomes or recycled via the Golgi apparatus. New or recycled receptors for LH are incorporated into the limiting membrane of protein containing secretory granules. One of the actions of LH is enhancement of the exocytosis of these secretory granules with incorporation of the limiting membrane (and the LH receptors?) of the granule into the plasma membrane of the cell. These proposed mechanisms explain the increase in the number of receptors for LH seen immediately after stimulation of the luteal cell with massive doses of LH and also explain the "down-regulation" of LH receptors 24 hr after administration of LH. PMID:6263609

  14. Inhibitory pathways and the inhibition of luteinizing hormone-releasing hormone release by alcohol

    PubMed Central

    Lomniczi, Alejandro; Mastronardi, Claudio A.; Faletti, Alicia G.; Seilicovich, Adriana; De Laurentiis, Andrea; McCann, Samuel M.; Rettori, Valeria

    2000-01-01

    In this research we examined the mechanisms by which ethanol (EtOH) inhibits luteinizing hormone-releasing hormone (LHRH) release from incubated medial basal hypothalamic explants. EtOH (100 mM) stimulated the release of two inhibitory neurotransmitters: γ-aminobutyric acid (GABA) and β-endorphin. EtOH also inhibited NO production, indicative of a suppression of nitric oxide synthase (NOS) activity. This inhibition was reversed by naltroxone (10−8 M), a μ-opioid receptor blocker, indicating that the inhibition of NOS by EtOH is mediated by β-endorphin. EtOH also blocked N-methyl-d-aspartic acid-induced LHRH release, but the blockade could not be reversed by either the GABA receptor blocker, bicuculline (10−5 M), naltroxone (10−8 M), or both inhibitors added together. However, increasing the concentration of naltrexone (10−6 M) but not bicuculline (10−4 M) reversed the inhibition. When we lowered the concentration of EtOH (50 mM), the EtOH-induced blockade of LHRH release could be reversed by either bicuculline (10−5 M), naltroxone (10−8 M), or the combination of the two blockers. Therefore, GABA is partially responsible for the blockade of N-methyl-d-aspartic acid-induced LHRH release. The block by GABA was exerted by inhibiting the activation of cyclooxygenase by NO, because it was reversed by prostaglandin E2, the product of activation of cyclooxygenase. Because the inhibition caused by the higher concentration of EtOH could not be reduced by bicuculline (10−4 M) but was blocked by naltroxone (10−6 M), the action of alcohol can be accounted for by stimulation of β-endorphin neurons that inhibit LHRH release by inhibition of activation of NOS and stimulation of GABA release. PMID:10688896

  15. Alcohol inhibits luteinizing hormone-releasing hormone release by activating the endocannabinoid system

    PubMed Central

    Fernández-Solari, Javier; Scorticati, Camila; Mohn, Claudia; De Laurentiis, Andrea; Billi, Silvia; Franchi, Ana; McCann, Samuel M.; Rettori, Valeria

    2004-01-01

    We hypothesized that ethanol (EtOH) might act through the endocannabinoid system to inhibit luteinizing hormone-releasing hormone (LHRH) release. Therefore, we examined the mechanism by which EtOH and anandamide (AEA), an endogenous cannabinoid, inhibit LHRH release from incubated medial basal hypothalamic explants. In previous work, we demonstrated that EtOH inhibits the N-methyl-d-aspartic acid-stimulated release of LHRH by increasing the release of two neurotransmitters: β-endorphin and γ-aminobutyric acid (GABA). In the present work, bicuculline, a GABAergic antagonist, completely prevented the inhibition of AEA (10-9M) on N-methyl-d-aspartic acid-induced LHRH release, but naltrexone, a μ-opioid receptor antagonist, had no effect. AEA also significantly increased GABA release but had no effect on β-endorphin release. Therefore, AEA could inhibit LHRH release by increasing GABA but not β-endorphin release. Because EtOH and AEA acted similarly to inhibit LHRH release, we investigated whether both substances would affect the adenylate cyclase activity acting through the same GTP-coupled receptors, the cannabinoid receptors 1 (CB1-rs). AEA and EtOH (10-1M) reduced the forskolin-stimulated accumulation of cAMP, but AM251, a specific antagonist of CB1-r, significantly blocked that inhibition. Additionally we investigated whether CB1-r is involved in the inhibition of LHRH by EtOH and AEA. AEA and EtOH reduced forskolin-stimulated LHRH release, but AM251 significantly blocked that inhibition. Also, we demonstrated that EtOH did not act by increasing AEA synthase activity to inhibit LHRH release in our experimental conditions. Therefore, our results indicate that EtOH inhibits the release of LHRH acting through the endocannabinoid system. PMID:14981261

  16. Efficacy of switching therapy of luteinizing hormone-releasing hormone analogue for advanced prostate cancer.

    PubMed

    Shen, Yuan-Chi; Kang, Chih-Hsiung; Chiang, Po-Hui

    2016-11-01

    This study was conducted to determine the efficacy of switching therapy with a second-line luteinizing hormone-releasing hormone (LHRH) analogue after prostate-specific antigen (PSA) progression for advanced prostate cancer. We enrolled 200 patients, from December 2005 to September 2013, with nodal positive, metastatic prostate cancer or disease progression after definite treatment receiving continuous LHRH analogue therapy with monthly depot leuprorelin(sc) acetate 3.75 mg/vial (LA) or goserelin acetate(sc) 3.6 mg/vial (GA). If the patients had castration-resistant prostate cancer, the treatment choice of switching therapy (from LA to GA or from GA to LA) prior to starting chemotherapy was given. The LH, testosterone level, and PSA change were recorded. The records showed that there were 127 patients receiving LA as initial ADT therapy, whereas the other 73 patients were in GA therapy. A total of 92 patients received LHRH analogue switching therapy (54 patients switched from LA to GA and 38 switched from GA to LA). The effect of LH and testosterone reduction prior to and after switching therapy was comparable between the two groups, and increased PSA level after 3 months of treatment was seen in both groups (median PSA: 15.7-67.7 ng/mL in the LA to GA group; 15.2-71.4 ng/mL in the GA to LA group). This study concluded that switching therapy for patients with PSA progression after ADT has no efficacy of further PSA response.

  17. Fertility in luteinizing hormone receptor-knockout mice after wild-type ovary transplantation demonstrates redundancy of extragonadal luteinizing hormone action

    PubMed Central

    Pakarainen, Tomi; Zhang, Fu-Ping; Poutanen, Matti; Huhtaniemi, Ilpo

    2005-01-01

    The luteinizing hormone receptor (LHR), mainly expressed in gonads, is essential for normal reproduction. However, numerous recent studies have also demonstrated LHR expression in multiple extragonadal reproductive and nonreproductive tissues. Although some effects of luteinizing hormone (LH) or its agonist, human chorionic gonadotropin, have been shown in extragonadal sites, their physiological significance remains open. In the present study, we have addressed the function of the extragonadal LHR using LHR-KO mice (LuRKO mice), in which the ovaries of prepubertal mice were orthotopically replaced with pieces of WT ovary using similarly transplanted WT mice as controls. Most ovarian transplants attained normal endocrine function in both groups of mice, as demonstrated by normal age at vaginal opening, estrous cycles, and sexual behavior. Both the LuRKO and WT mice repeatedly became pregnant (9/16 vs. 16/20 after first mating; difference not significant) and delivered similarly sized litters, which grew normally after birth, indicating normal lactation. In conclusion, fertility is restored in LuRKO mice by transplantation of WT ovarian tissue. This is achieved in the absence of extragonadal LHR expression, which indicates physiological redundancy for such receptor sites. PMID:15951841

  18. The purification of luteinizing-hormone-releasing factor with some observations on its properties

    PubMed Central

    Fawcett, C. P.; Reed, May; Charlton, H. M.; Harris, G. W.

    1968-01-01

    Bullock median-eminence tissue was used as a source of luteinizing-hormone-releasing factor for small-scale experiments to explore methods for its isolation. The presence of luteinizing-hormone-releasing factor was detected by the ovulation response in rabbits after intrapituitary infusion of the extract. Gel filtration was found to be suitable for the purification of these extracts. The releasing factor appeared to be a basic peptide of molecular weight in the range 1200–2500. On a larger scale, an extract of hypothalamic tissue from sheep was used to establish a multi-stage isolation procedure that resulted in a 200000-fold purification of luteinizing-hormone-releasing factor. After the initial extraction the isolation process consisted of: (1) two cycles of gel filtration; (2) anion-exchange chromatography; (3) gel filtration in a partially organic medium; (4) thin-layer chromatography on cellulose. Stage (3) separated two zones of activity each containing peptides. One of these was purified further by stage (4) to give a preparation that was active at a dose of 6μg. of peptide/animal, although activity diminished seriously during storage. This preparation contained only five or six components, but the small amounts of peptides obtained at this stage of purity were insufficient for full characterization. ImagesFig. 5. PMID:4889362

  19. Activation of GABA B receptors in the anterior pituitary inhibits prolactin and luteinizing hormone secretion.

    PubMed

    Lux-Lantos, V; Rey, E; Libertun, C

    1992-11-01

    Previous work from our laboratory showed that baclofen could lower serum prolactin (PRL) levels acting at the central nervous system. The present experiments were designed to evaluate whether the gamma-aminobutyric acid B agonist was also effective in inhibiting hormone release at the pituitary level. In monolayer cultures of adenohypophyseal dispersed cells, baclofen inhibited basal PRL secretion after 1 or 2 h of incubation. This inhibition was significantly abolished by three antagonists: phaclofen, 3-aminopropyl-phosphonic acid and 4-aminobutylphosphonic acid. Furthermore, baclofen inhibited the thyrotropin-releasing hormone-induced PRL release in a concentration-dependent manner. With regard to gonadotropin secretion, baclofen was unable to modify basal luteinizing hormone (LH) secretion, but significantly inhibited the LH-releasing hormone-induced LH release. These results show that baclofen, in addition to its central neuroendocrine effects, inhibits pituitary hormone secretion, under basal and/or stimulated conditions, by direct action at the pituitary level.

  20. Chronic effects of marihuana smoking on luteinizing hormone, follicle-stimulating hormone and prolactin levels in human males.

    PubMed

    Vescovi, P P; Pedrazzoni, M; Michelini, M; Maninetti, L; Bernardelli, F; Passeri, M

    1992-04-01

    The purpose of this investigation was to assess the chronic effects of marihuana smoking on the basal and stimulated secretion of the pituitary hormones luteinizing hormone (LH), follicle-stimulating (FSH) and prolactin (PRL). Ten male chronic marihuana users and 10 age- and sex-matched healthy volunteers were studied by measuring hormone levels before and after i.v. administration of thyrotropin releasing hormone (TRH) and gonadotropin releasing hormone (GnRH). The basal and stimulated levels of LH were reduced in marihuana users, whereas FSH and PRL levels and responses were not different from the control subjects. The chronic use of marihuana may selectively impair the hypothalamic control mechanisms regulating LH secretion.

  1. Male rats secrete luteinizing hormone and testosterone episodically.

    PubMed

    Ellis, G B; Desjardins, C

    1982-05-01

    We studied the temporal aspects of endocrine signaling between the pituitary gland and testes by measuring moment to moment changes in blood LH and testosterone levels in individual male rats. Each rat was fitted with an indwelling vascular cannula, and blood was withdrawn every 5 min for 8-12 h. Rats were maintained throughout the intensive blood-sampling period with an isotonic blood replacement mixture containing rat red blood cells and a human plasma protein preparation. LH and testosterone measurements were made in plasma volumes of 50 and 60 microliters. Most rats released LH in well defined pulses, characterized by a rapid increase in plasma LH within 5-10 min and a gradual decline lasting for the next 50-70 min. LH pulses occurred singly or in trains of two to four. Episodes of testosterone secretion spanned 3-6 h and were marked by a slowly graded rise and fall of plasma testosterone. In several instances, testosterone episodes were preceded (1-2 h) by a train of closely coupled LH pulses. Within a particular animal on different days, hormone episodes varied in number, amplitude, and timing. A particular hormone profile did not serve as a reliable hormone signature for an individual rat. Many rats displayed a characteristic sequence of 1) multiple LH pulses, 2) a sustained testosterone episode, and 3) a period of no LH pulses. This tripartite sequence of events is viewed as the essence of pituitary-testicular stimulation, and testicular negative feedback. Intermittent, short term fluctuations in peripheral levels of LH and testosterone represent the blood-borne, gland to gland signals controlling hypothalamic-pituitary-testicular function in the normal rat.

  2. Reproductive characteristics of grass-fed, luteinizing hormone-releasing hormone-immunocastrated Bos indicus bulls.

    PubMed

    Hernandez, J A; Zanella, E L; Bogden, R; de Avila, D M; Gaskins, C T; Reeves, J J

    2005-12-01

    Two field trials were conducted in Brazil to evaluate LHRH immunocastration of Bos indicus bulls (d 0 = 2 yr of age). In Study I, 72 bulls were assigned randomly to one of three treatment groups: LHRH0-immunized, castrated, and intact. Immunized animals (n = 25) received a primary and two booster injections of ovalbumin-LHRH-7 and thioredoxin-LHRH-7 fusion proteins on d 0, 141, and 287. Twenty-three bulls were surgically castrated on d 141, and 24 served as intact controls. All animals were slaughtered on d 385, at approximately 3 yr of age. In Study II, 216 bulls were assigned randomly to the same three treatments as in Study I; however, because of a drought in the area, bulls were kept on pasture an additional year, and a fourth treatment was added, in which one-half the LHRH-immunized bulls received an additional booster on d 639 (fourth immunization). All animals in Study II were slaughtered on d 741 (4 yr of age). Luteinizing hormone-releasing hormone antibodies increased following each immunization for immunized bulls, but they were not detectable in castrate or intact animals in either study. Consequently, scrotal circumference was suppressed in immunized bulls compared with intact controls in both studies. By d 287, serum concentrations of testosterone in LHRH-immunized bulls were decreased compared with intact controls (P < 0.01). In both studies, testes and epididymal weights at slaughter were greater (P < 0.01) for intact (500 +/- 17 and 60 +/- 2 g, respectively) than for immunized bulls (173 +/- 22 and 26 +/- 2 g, respectively) and fourth immunization bulls (78 +/- 23 and 20 +/- 2 g, respectively; Study II). At the end of each study, BW was greater (P < 0.01) for intact bulls than for castrated and LHRH-immunized animals. In these two studies, the efficacy of the LHRH fusion proteins to induce an effect similar to that of surgical castration was considered 92 and 93%, respectively. These data support the concept that immunocastration of bulls at 2 yr of

  3. Requirement for specific gravity and creatinine adjustments for urinary steroids and luteinizing hormone concentrations in adolescents.

    PubMed

    Singh, Gurmeet K S; Balzer, Ben W R; Desai, Reena; Jimenez, Mark; Steinbeck, Katharine S; Handelsman, David J

    2015-11-01

    Urinary hormone concentrations are often adjusted to correct for hydration status. We aimed to determine whether first morning void urine hormones in growing adolescents require adjustments and, if so, whether urinary creatinine or specific gravity are better adjustments. The study population was adolescents aged 10.1 to 14.3 years initially who provided fasting morning blood samples at 0 and 12 months (n = 343) and first morning urine every three months (n = 644). Unadjusted, creatinine and specific gravity-adjusted hormonal concentrations were compared by Deming regression and Bland-Altman analysis and grouped according to self-rated Tanner stage or chronological age. F-ratios for self-rated Tanner stages and age groups were used to compare unadjusted and adjusted hormonal changes in growing young adolescents. Correlations of paired serum and urinary hormonal concentration of unadjusted and creatinine and specific gravity-adjusted were also compared. Fasting first morning void hormone concentrations correlated well and were unbiased between unadjusted or adjusted by either creatinine or specific gravity. Urine creatinine concentration increases with Tanner stages, age and male gender whereas urine specific gravity was not influenced by Tanner stage, age or gender. Adjustment by creatinine or specific gravity of urinary luteinizing hormone, estradiol, testosterone, dihydrotestosterone and dehydroepiandrosterone concentrations did not improve correlation with paired serum concentrations. Urine steroid and luteinizing hormone concentrations in first morning void samples of adolescents are not significantly influenced by hydration status and may not require adjustments; however, if desired, both creatinine and specific gravity adjustments are equally suitable. © The Author(s) 2015.

  4. Luteinizing hormone promotes gonadal tumorigenesis in inhibin-deficient mice

    PubMed Central

    Nagaraja, Ankur K.; Agno, Julio E.; Kumar, T. Rajendra; Matzuk, Martin M.

    2009-01-01

    Summary The inhibins are secreted α:β heterodimers of the TGF-β superfamily that are mainly synthesized in Sertoli cells and granulosa cells, and are critical regulators of testicular and ovarian development and function. Mice homozygous for a targeted deletion of the inhibin α subunit gene (Inha-/-) develop sex cord-stromal tumors in a gonadotropin-dependent manner. Here, we determine the contribution of LH to gonadal tumorigenesis by generating mice deficient in both inhibins and LH. Inha-/-Lhb-/- mice have increased survival and delayed tumor progression, and these observations correlate with lower serum FSH and estradiol levels compared to Inha-/- controls. Double mutant testicular tumors demonstrate decreased expression of cyclin D2, while double mutant ovarian tumors have elevated expression of p15INK4b and trend toward higher levels of p27Kip1. We conclude that LH is not required for tumor formation in the absence of inhibins but promotes tumor progression, likely through alterations in serum hormone levels and cell cycle regulators. PMID:18657590

  5. Metabolism of testosterone by human granulosa cells in culture: influence of follicle-stimulating hormone and luteinizing hormone

    SciTech Connect

    Moon, Y.S.; Duleba, A.; Leung, P.C.; Gomel, V.

    1982-03-15

    Human granulosa cells were isolated from follicles (8 to 15 mm) and cultivated for 24 hours in the presence or absence of follicle-stimulating hormone (NIH-FSH-HS-1, 1 microgram/ml) and luteinizing hormone (NIAMDD-hLH-1, 1 microgram/ml). Testosterone -4-14C was added subsequently to all cultures for 4-, 6-, and 24-hour periods. Of the seven metabolites of testosterone studied, 17 beta-estradiol (E2) and estrone (E1) were the major products. In all patients, levels of E2 were three to ten times higher than those of E1. Production of E2, but not E1, was stimulated by either follicle-stimulating hormone (FSH) or luteinizing hormone (LH). The cells of the largest follicle (15 mm) showed greater response to LH than to FSH. Production of the other C19 and C18 metabolites was very low or negligible. These results further suggest that FSH regulates the aromatization of testosterone in human granulosa cells, and that LH may have the same effect on the matured follicle during the preovulatory period.

  6. Progression of intracranial meningioma during luteinizing hormone-releasing hormone agonist treatment for prostate cancer: case report.

    PubMed

    Anda, Takeo; Honda, Masaru; Ishihara, Tokuhiro; Kamei, Toshiaki

    2014-01-01

    The authors describe a male patient who developed a large intracranial meningioma during the hormone therapy for pre-existing prostate cancer. A 70-year-old man received a brain check-up, and no intracranial abnormality was detected. Five months later, prostate cancer was diagnosed, and he underwent prostatectomy. Leuprorelin acetate, a luteinizing hormone-releasing hormone (LH-RH) agonist, was subsequently administered to the patient once a month for 3 years. After that he presented with a large parasagittal mass, which was excised. The tumor was histologically diagnosed as meningothelial meningioma, and LH-RH receptors were verified immunohistochemically in the cytoplasm of the tumor cells. Leuprorelin acetate may accelerate the rapid growth of meningioma in this patient.

  7. Progression of Intracranial Meningioma during Luteinizing Hormone-Releasing Hormone Agonist Treatment for Prostate Cancer: Case Report

    PubMed Central

    ANDA, Takeo; HONDA, Masaru; ISHIHARA, Tokuhiro; KAMEI, Toshiaki

    2014-01-01

    The authors describe a male patient who developed a large intracranial meningioma during the hormone therapy for pre-existing prostate cancer. A 70-year-old man received a brain check-up, and no intracranial abnormality was detected. Five months later, prostate cancer was diagnosed, and he underwent prostatectomy. Leuprorelin acetate, a luteinizing hormone-releasing hormone (LH-RH) agonist, was subsequently administered to the patient once a month for 3 years. After that he presented with a large parasagittal mass, which was excised. The tumor was histologically diagnosed as meningothelial meningioma, and LH-RH receptors were verified immunohistochemically in the cytoplasm of the tumor cells. Leuprorelin acetate may accelerate the rapid growth of meningioma in this patient. PMID:24201100

  8. Organophosphorus insecticide induced decrease in plasma luteinizing hormone concentration in white-footed mice

    USGS Publications Warehouse

    Rattner, B.A.; Michael, S.D.

    1985-01-01

    Oral intubation of 50 and 100 mg/kg acephate inhibited brain acetylcholinesterase (AChE) activity by 45% and 56%, and reduced basal luteinizing hormone (LH) concentration by 29% and 25% after 4 h in white-footed mice (Peromyscus leucopus noveboracensis). Dietary exposure to 25, 100, and 400 ppm acephate for 5 days substantially inhibited brain AChE activity, but did not affect plasma LH concentration. These preliminary findings suggest that acute exposure to organophosphorus insecticides may affect LH secretion and possibly reproductive function.

  9. Leap of Faith: Does serum luteinizing hormone always accurately reflect central reproductive neuroendocrine activity?

    PubMed Central

    Moenter, Suzanne M.

    2015-01-01

    Function of the central aspects of the hypothalamo-pituitary-gonadal axis has been assessed in a number of ways including direct measurements of hypothalamic output and indirect measures using gonadotropin release from the pituitary as a bioassay for reproductive neuroendocrine activity. Here, methods for monitoring these various parameters are briefly reviewed and then examples presented of both concordance and discrepancy between central and peripheral measurements, with a focus on situations in which elevated GnRH neurosecretion is not reflected accurately by pituitary luteinizing hormone release. Implications for interpretation of gonadotropin data are discussed. PMID:26278916

  10. Topographical localization of the receptors for luteinizing hormone- releasing hormone on the surface of dissociated pituitary cells

    PubMed Central

    1977-01-01

    A derivative of the hypothalamic peptide luteinizing hormone-releasing hormone (LHRH) has been coupled to ferritin and the conjugate purified by gel chromatography. In its ability to stimulate the secretion of luteinizing hormone from pituitary cells in vitro, the conjugate has the same potency and specificity as the native peptide. When dissociated pituitary cells maintained in short-term culture are lightly fixed with formaldehyde and then incubated with the conjugate, examination in the electron microscope shows an even distribution of ferritin particles over the free cell surface of the gonadotrophin cells. This binding appears to be specific for the LHRH receptor since it is prevented by a 10-fold excess of native peptide. In addition to the gonadotrophin cells, some somatotrophin and thyrotrophin cells bind conjugate on their free surfaces under similar conditions. If living cells are incubated with the conjugate for 15 min, the bound conjugate becomes aggregated and then concentrated in one localized area of the cell surface. In this area, which lies immediately above the juxtanuclear Golgi complex, the plasma membrane is frequently invaginated in a manner which suggests that the bound, aggregated conjugate is internalized by endocytosis. PMID:233747

  11. Effects of a luteinizing hormone-releasing hormone agonist on cognitive, sexual, and hormonal functions in patients with prostate cancer: relationship with testicular and adrenal androgen levels.

    PubMed

    Okamoto, Kohei; Sekine, Yositaka; Nomura, Masashi; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Ito, Kazuto; Suzuki, Kazuhiro

    2015-01-01

    To assess the cognitive and sexual/hormonal functioning of prostate cancer patients treated with a luteinizing hormone-releasing hormone (LH-RH) agonist, and the relationships thereof with adrenal and residual testicular androgen levels. Previously, we reported the effect of a luteinizing hormone-releasing hormone (LH-RH) agonist on testicular and adrenal androgen production in patients with prostate cancer. A 6-month treatment with an LH-RH agonist significantly reduced testicular androgens by 90-95% and adrenal androgens by 26-40%. This study evaluated the changes in cognitive and sexual/hormonal functions in the same cohort using the Mini-Mental State Evaluation (MMSE) and Expanded Prostate Cancer Index Composite (EPIC) questionnaire, respectively. In addition, the associations of each function with the serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2), dehydroepiandrosterone-sulfate (DHEA-S), dehydroepiandrosterone (DHEA), androstenedione (A-dione), and cortisol levels were studied. Cognitive functions did not change significantly during the treatment. Sexual functions were relatively low before treatment and worsened significantly after 6 and 12 months of treatment. Interestingly, sexual bothers were improved with the treatment. The treatment significantly worsened hormonal functions and bothers. Regarding specific items in the hormonal domains, hot flashes and body weight changes were the main effects of worsened hormonal function. Low levels of T and E2 and high levels of A-dione were associated with low MMSE scores at 6 months. Regarding sexual and hormonal functions, A-dione, E2, T, cortisol, and DHEA-S were associated with poorer functioning and bother. Especially, low T levels and high E2 levels were the most significant factors associated with worse sexual and hormonal bothers. The LH-RH agonist monotherapy worsened sexual and hormonal functions and hormonal bothers, but not sexual bothers or cognitive functions. The changes in these

  12. Cyclical secretion of prorenin during the menstrual cycle: synchronization with luteinizing hormone and progesterone.

    PubMed Central

    Sealey, J E; Atlas, S A; Glorioso, N; Manapat, H; Laragh, J H

    1985-01-01

    Plasma prorenin, a high molecular weight precursor form of renin, (renin, EC 3.4.23.15; old number, EC 3.4.99.19), was measured three times weekly in normal young women during the menstrual cycle and was related to changes in luteinizing hormone, estradiol, and progesterone. In all subjects a stable baseline level of prorenin occurred during the follicular phase. Then, simultaneously or soon after the luteinizing hormone peak, plasma prorenin consistently increased about 2-fold. Baseline prorenin ranged from 18 to 40 ng per ml per hr, and peak prorenin ranged from 35 to 65 ng per ml per hr. The maximum increase in prorenin averaged 80%. Prorenin remained elevated during the mid-luteal phase of the menstrual cycle and returned to baseline during the late-luteal phase in coordination with the decrease in progesterone. The changes in prorenin were not synchronized with changes in active renin which was significantly increased only during the mid-luteal phase. These findings suggest that prorenin may be involved in reproductive physiology. PMID:3909151

  13. The effect of luteinizing hormone releasing hormone analog regime and stage of oocyte maturity for induced ovulation of channel catfish Ictalurus punctatus

    USDA-ARS?s Scientific Manuscript database

    The effective LHRHa (luteinizing hormone releasing hormone analog) dose based on the gonadal maturity of channel catfish, Ictalurus punctatus to optimize channel x blue hybrid catfish production was evaluated in 4 trials (twice in early part of the season and twice in the peak spawning season) in a ...

  14. Luteinizing hormone modulates intracellular calcium, protein tyrosine phosphorylation and motility during human sperm capacitation.

    PubMed

    López-Torres, Aideé S; González-González, María E; Mata-Martínez, Esperanza; Larrea, Fernando; Treviño, Claudia L; Chirinos, Mayel

    2017-02-05

    In order to fertilize, spermatozoa must undergo physiological and biochemical changes during their transit along the female reproductive tract before reaching and fusing with the oocyte, process known as capacitation. Sperm modifications associated with capacitation are modulated by their interaction with molecules present in the female reproductive tract. During the woman fertile window, some reproductive hormones reach their maximum concentrations in serum, such as the luteinizing hormone (LH). Since spermatozoa preparing to fertilize may be exposed to LH, the purpose of this work was to study the effects of this hormone on intracellular Ca(2+) concentrations ([Ca(2+)]i), protein tyrosine phosphorylation, sperm motility and acrosome reaction under capacitating conditions. The results showed that LH increases the duration and amplitude of Ca(2+) oscillations. Furthermore, motility analysis indicated that LH decreases rapid progressive motility and that sperm hyperactivation as well as several kinetic parameters augment in the presence of 0.5 and 1 μg/ml of the hormone. In addition, these two hormone concentrations also consistently promoted protein tyrosine phosphorylation. However, no effects on acrosome reaction were observed. In conclusion, the evidence indicates that LH modulates several sperm function variables involved in capacitation, suggesting that may have an important and unexplored role during human fertilization. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Luteinizing hormone-releasing hormone (LH-RH) as a diagnostic and research tool in gynecologic endocrinology.

    PubMed

    Taymor, M L; Thompson, I E; Berger, M J; Patton, W

    1974-11-15

    A study is reported on the effects of 150 mcg. of luteinizing hormone-releasing hormone (LH-RH), administered iv to 48 women with 5 types of secondary oligoamenorrhea, on the serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Levels. At Time 0, patients with pituitary disease showed a markedly diminished LH response and patients with polycystic ovarian disease with enlarged ovaries showed a brisk, elevated LH response. FSH levels in patients with pituitary disease and polycystic ovarian disease showed a negligible rise at Time 0. 9 of 10 patients with pituitary disease and 5 of 9 patients with dietary amenorrhea had a low LH response 30 minutes after LH-RH administration. FSH response 60 minutes after injection in patients with pituitary disease and polycystic ovarian disease seemed to be lowered though too much overlap prevented a complete diagnosis. The conclusion of this initial study is that through baseline determinations of FSH and LH, along with a LH-RH stimulation test, useful data are provided for determining whether amenorrhea is due to ovarian or pituitary failure. A 2nd study evaluated the effects of 150 mcg of LH-RH administered iv before and after the im administration of various dosages of estrogen and progesterone to anovulatory women. A vigorous response in pituitary gonadotropin, particularly LH, was observed with LH-RH administered only. The effect with estrogen and progesterone was diminished pituitary response in terms of LH production. It is concluded that estrogen and progesterone exert a negative feedback effect on gonadotropin secretion at the hypothalamic and pituitary levels.

  16. Effects of peppermint teas on plasma testosterone, follicle-stimulating hormone, and luteinizing hormone levels and testicular tissue in rats.

    PubMed

    Akdogan, Mehmet; Ozguner, Meltem; Kocak, Ahmet; Oncu, Meral; Cicek, Ekrem

    2004-08-01

    To justify the effects of Mentha piperita labiatae and Mentha spicata labiatae herbal teas on plasma total testosterone, luteinizing hormone, and follicle-stimulating hormone levels and testicular histologic features. We performed this study because of major complaints in our area from men about the adverse effects of these herbs on male reproductive function. The experimental study included 48 male Wistar albino rats (body weight 200 to 250 g). The rats were randomized into four groups of 12 rats each. The control group was given commercial drinking water, and the experimental groups were given 20 g/L M. piperita tea, 20 g/L M. spicata tea, or 40 g/L M. spicata tea. The follicle-stimulating hormone and luteinizing hormone levels had increased and total testosterone levels had decreased in the experimental groups compared with the control group; the differences were statistically significant. Also, the Johnsen testicular biopsy scores were significantly different statistically between the experimental groups and the control group. Although the mean seminiferous tubular diameter of the experimental groups was relatively greater than in the control group, the difference was not statistically significant. The only effects of M. piperita on testicular tissue was segmental maturation arrest in the seminiferous tubules; however, the effects of M. spicata extended from maturation arrest to diffuse germ cell aplasia in relation to the dose. Despite the beneficial effects of M. piperita and M. spicata in digestion, we should also be aware of the toxic effects when the herbs are not used in the recommended fashion or at the recommended dose.

  17. Evaluation of the Biological Properties and the Enzymatic Stability of Glycosylated Luteinizing Hormone-Releasing Hormone Analogs.

    PubMed

    Moradi, Shayli Varasteh; Varamini, Pegah; Toth, Istvan

    2015-09-01

    The enzymatic stability, antitumor activity, and gonadotropin stimulatory effects of glycosylated luteinizing hormone-releasing hormone (LHRH) analogs were investigated in this study. Conjugation of carbohydrate units, including lactose (Lac), glucose (GS), and galactose (Gal) to LHRH peptide protected the peptide from proteolytic degradation and increased the peptides' half-lives in human plasma, rat kidney membrane enzymes, and liver homogenate markedly. Among all seven modified analogs, compound 1 (Lac-[Q(1)][w(6)]LHRH) and compound 6 (GS(4)-[w(6)]LHRH) were stable in human plasma during 4 h of experiment. The half-lives of compounds 1 and 6 improved significantly in kidney membrane enzymes (from 3 min for LHRH to 68 and 103 min, respectively). The major cleavage sites for most of the glycosylated compounds were found to be at Trp(3)-Ser(4) and Ser(4)-Tyr(5) in compounds 1-5. Compound 6 was hydrolyzed at Ser(4)-Tyr(5) and the sugar conjugation site. The antiproliferative activity of the glycopeptides was evaluated on LHRH receptor-positive prostate cancer cells. The glycosylated LHRH derivatives had a significant growth inhibitory effect on the LNCaP cells after a 48-h treatment. It was demonstrated that compound 1 significantly increased the release of luteinizing hormone (LH) at 5 and 10 nM concentrations and compound 5 (GS-[Q(1)]LHRH) stimulated the release of follicle-stimulating hormone (FSH) at 5 nM concentration in dispersed rat pituitary cells (p < 0.05). In our studies, compound 1-bearing lactose and D-Trp was the most stable and active and is a promising candidate for future preclinical investigations in terms of in vitro biological activity and metabolic stability.

  18. Search for novel therapies for triple negative breast cancers (TNBC): analogs of luteinizing hormone-releasing hormone (LHRH) and growth hormone-releasing hormone (GHRH).

    PubMed

    Buchholz, Stefan; Seitz, Stephan; Engel, Jörg B; Montero, Alberto; Ortmann, Olaf; Perez, Roberto; Block, Norman L; Schally, Andrew V

    2012-04-01

    Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that is clinically negative for the expression of estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor-2 (HER2). Patients with TNBC have a worse clinical outcome, as measured by time to metastasis and median overall survival. Chemotherapy has been the mainstay of treatment of TNBC but responses are disappointing. A substantial proportion of TNBC expresses luteinizing hormone-releasing hormone (LHRH), receptors for LHRH, in addition to receptors for growth hormone-releasing hormone (GHRH). These receptors represent potential therapeutic targets. Potent antagonists of GHRH and LHRH receptors have been developed in recent years and these antagonists inhibit the growth, tumorigenicity and metastatic potential of various human experimental malignancies. These antagonists could be utilized for the treatment of TNBC. The targeted cytotoxic analog of LHRH, AN-152 (AEZS-108) containing doxorubicin, must also be strongly considered for therapy of TNBC. Experimental studies suggest the merit of clinical trials with LHRH antagonists and AEZS-108 in TNBC patients.

  19. Wood duck hatch date: relationship to pairing chronology, plasma luteinizing hormone, and steroid hormones during autumn and winter.

    PubMed

    Hepp, G R; Connolly, P; Kennamer, R A; Harvey, W F

    1991-06-01

    We examined variation in courtship activity and hormone levels of male and female wood ducks (Aix sponsa) in relation to hatch date. Young wood ducks were assigned in groups of 8 (4 males and 4 females) to 4 experimental pens; 2 pens contained early-hatched ducks (3-12 April) and 2 pens contained late-hatched ducks (7-16 June). Courtship behaviors occurred less frequently in October and November than in December and January-February for both early- and late-hatched groups. Early-hatched wood ducks participated in courtship more frequently and formed pair bonds sooner than late-hatched individuals. Testosterone (T) and androstenedione (AD) levels of males did not differ between treatment groups; however, average levels of luteinizing hormone (LH) were greater for early-hatched males. Differences in LH occurred in 2 of 12 samples (6 October and 3 November); otherwise, LH did not vary by treatment. Levels of T and LH in males varied temporally, but there was no significant temporal variation in AE levels. Temporal variation in hormone levels was similar for early- and late-hatched males. Estradiol (E), progesterone (P), and LH levels of females did not differ between treatment groups. There was temporal variation in levels of E and LH, but not of P; this variation was similar for early- and late-hatched females. These data indicate that behavioral differences occurring temporally and between early- and late-hatched wood ducks were not related to corresponding differences in hormone levels.

  20. Effect of naloxone treatment on luteinizing hormone and testosterone concentrations in boars with high and low libido

    USDA-ARS?s Scientific Manuscript database

    The objective was to determine the effects of naloxone, an opioid peptide receptor antagonist on circulating concentrations of luteinizing hormone (LH) and testosterone in boars characterized as having high (n = 8) or low libido (n = 8) based on the willingness to mount an artificial sow and allow s...

  1. Fish eggs as bioreactors: the production of bioactive luteinizing hormone in transgenic trout embryos.

    PubMed

    Morita, Tetsuro; Yoshizaki, Goro; Kobayashi, Makito; Watabe, Shugo; Takeuchi, Toshio

    2004-12-01

    We demonstrated the production of goldfish luteinizing hormone (gfLH) by the use of 4-day-old rainbow trout embryos as novel bioreactors. This expression system has several advantages: target proteins can be rapidly expressed at low cost, and recombinant proteins can be synthesized at low temperatures and can undergo complex post-translational modifications (PTMs). An expression vector containing gfLH cDNA was microinjected into fertilized trout eggs. After 4 days of incubation at 10 degrees C, transgenic embryos were harvested and glycosylated recombinant gfLH was recovered, which stimulated testosterone production in testicular fragments from the goldfish. This is the first report on the successful production of bioactive recombinant gonadotropin originated from cyprinid. Further, these results demonstrate that trout-embryo bioreactors are a potentially powerful tool for the production of functional recombinant proteins.

  2. Depression of plasma luteinizing hormone concentration in quail by the anticholinesterase insecticide parathion

    USGS Publications Warehouse

    Rattner, B.A.; Clarke, R.N.; Ottinger, M.A.

    1986-01-01

    1. To examine the effects of parathion on basal plasma luteinizing hormone (LH) concentration, male Japanese quail (Coturnix japonica) were orally intubated with 0, 5 or 10 mg/kg parathion and sacrificed after 4, 8 and 24 hr.2. At the 5 mg/kg dose, plasma LH levels were reduced at 4 and 8 hr, but returned to control values by 24 hr. Brain acetylcholinesterase activity was substantially reduced by 10 mg/kg parathion (52, 75 and 37% inhibition at 4, 8 and 24 hr, respectively) and plasma LH concentration remained depressed through the 24-hr period.3. These findings suggest that the organophosphorus insecticide parathion may alter plasma LH concentration in a manner which might impair reproductive activity, and provide indirect evidence for a cholinergic component in the regulation of LH secretion in quail.

  3. Luteinizing hormone receptors in human ovarian follicles and corpora lutea during the menstrual cycle

    SciTech Connect

    Yamoto, M.; Nakano, R.; Iwasaki, M.; Ikoma, H.; Furukawa, K.

    1986-08-01

    The binding of /sup 125/I-labeled human luteinizing hormone (hLH) to the 2000-g fraction of human ovarian follicles and corpora lutea during the entire menstrual cycle was examined. Specific high affinity, low capacity receptors for hLH were demonstrated in the 2000-g fraction of both follicles and corpora lutea. Specific binding of /sup 125/I-labeled hLH to follicular tissue increased from the early follicular phase to the ovulatory phase. Specific binding of /sup 125/I-labeled hLH to luteal tissue increased from the early luteal phase to the midluteal phase and decreased towards the late luteal phase. The results of the present study indicate that the increase and decrease in receptors for hLH during the menstrual cycle might play an important role in the regulation of the ovarian cycle.

  4. Depression of plasma luteinizing hormone concentration in quail by the anticholinesterase insecticide parathion

    USGS Publications Warehouse

    Rattner, B.A.; Clarke, R.N.; Ottinger, M.A.

    1986-01-01

    To examine the effects of parathion on basal plasma luteinizing hormone (LH) concentration, male Japanese quail (Coturnix japonica) were orally intubated with 0, 5 or 10 mg/kg parathion and sacrificed after 4, 8 and 24 hr. At the 5 mg/kg dose, plasma LH levels were reduced at 4 and 8 hr, but returned to control values by 24 hr. Brain acetylcholinesterase activity was substantially reduced by 10 mg/kg parathion (52, 75 and 37% inhibition at 4, 8 and 24 hr, respectively) and plasma LH concentration remained depressed through the 24-hr period. These findings suggest that the organophosphorus insecticide parathion may alter plasma LH concentration in a manner which might impair reproductive activity, and provide indirect evidence for a cholinergic component in the regulation of LH secretion in quail.

  5. Luteinizing hormone releasing factor in rat hypophysial portal blood collected during electrical stimulation of the hypothalamus

    PubMed Central

    Harris, G. W.; Ruf, K. B.

    1970-01-01

    1. Ovulation was induced in Nembutal-blocked pro-oestrous rats by electrical stimulation of the hypothalamus. 2. The same type of electrical stimulation was applied during the collection of hypophysial portal blood. 3. Pooled hypophysial portal plasma from donors in pro-oestrus, oestrus and met-oestrus was assayed for ovarian ascorbic acid depleting (OAAD) activity. 4. Electrical stimulation of the hypothalamus increased the OAAD activity, believed to be due to luteinizing hormone releasing factor (LRF), in pro-oestrus and met-oestrus, but not in oestrus. 5. It is concluded that the hypothalamic nerve fibres responsible for releasing LRF into the hypophysial portal vessels are depleted of their store of this releasing factor, or are refractory to electrical stimulation, during oestrus. PMID:5499765

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

    PubMed Central

    Folkers, K; Bowers, C Y; Tang, P F; Kubota, M

    1986-01-01

    Apparently, no agonist has been found that is comparable in potency to the luteinizing hormone-releasing hormone (LHRH) for release of LH and follicle-stimulating hormone (FSH) without substitutions with unnatural or D forms of natural amino acids. Of 139 known "agonist analogs" of LHRH, two were active in the range of 65%. The four LHRHs known to occur in nature involve a total of six amino acids (Tyr, His, Leu, Trp, Arg, Gln) in positions 5, 7, and 8. There are 16 possible peptides with these six amino acids in positions 5, 7, and 8, of which 4 are the known LHRHs, and 2 more were synthesized. We have synthesized the 10 new peptides and assayed 11 in vivo and in vitro, and we found not only 1 but a total of 5 that have activity equivalent to or greater than that of LHRH for the release of LH and/or FSH under at least one assay condition. These five are as follows: [His5,Trp7,Gln8]LHRH; [His5,Trp7,Leu8]LHRH; [His5,Trp7]LHRH; [Trp7]LHRH; [His5]LHRH. Two of these five agonists variably released relatively more FSH than LH. One or more of these five agonists may occur in nature and one may be follicle-stimulating hormone-releasing hormone. The two peptides with Gln8 and Leu8, if occurring in nature, may have different receptors according to radioreceptor assays and to the ratio of LH/FSH release in vivo. These structures are a basis for the design of antagonists without Arg8 toward avoiding histamine release. Complete inhibition of LH and FSH release in vivo may be induced by joint use of Arg8 and Gln8 or Leu8 antagonists. These potent agonists, related to LHRH, may be therapeutically useful in disorders of reproduction, the central nervous system, and for the control of hormone-dependent carcinomas. PMID:3081889

  7. Luteinizing hormone, progesterone and the morphological development of normal and superovulated corpora lutea in sheep.

    PubMed

    McClellan, M C; Dieckman, M A; Abel, J H; Niswender, G D

    1975-12-10

    The development of granulosa-lutein cells was studied in 27 normal and 32 superovulated ewes between days 0-4(day 0 began with the preovulatory LH peak in normal animals and the HCG injection in superovulated ewes). The pattern of differentiation was similar in both groups. Following initial hormonal stimulation (0-12 hours after LH or HCG), granulosa cells were approximately 100 mu2 and contained small, pleomorphic nuclei with large amounts of clumped chromatin. Elongate cells lining the basement membrane possessed large, heterogeneous dense bodies, and a well-developed Golgi apparatus. Mitotic figures were observed up to 6 hours prior to ovulation. Sixteen to 20 hours following the LH surge or HCG injection, hypertrophy of granulosa cells was evident. Nuclei contained definitive nucleoli. Blood vessels in the theca interna were abundant and highly dilated. Ovulation occurred approximately 24 hours after the LH peak or HCG injection. Visible signs of luteinization were evident 6-12 hours after ovulation. A slight increase in serum progesterone levels was detected. The second post-ovulatory day was characterized by continuing hypertrophy of granulosa cells and extensive proliferation of smooth endoplasmic reticulum and mitochondria. Nuclei of granulosa cells were larger and possessed extremely large nucleoli. Numerous mitotic figures were apparent within the corpus luteum. Serum progesterone concentrations began increasing at 60-72 hours after hormone stimulation. By the end of the third post-ovulatory day, the corpus luteum consisted of large, pleomorphic, parenchymal cells, interspersed between capillaries and connective tissue elements. Only an occasional mitotic figure was apparent within the corpus luteum at 100 hours. Light microscopic autoradiography of 5, 10, and 15 day corpora lutea taken from ewes pulsed with 3H thymidine at specific times before and after ovulation revealed that granulosa cells did not undergo secondary mitoses following ovulation. In

  8. Influence of luteinizing hormone support on granulosa cells transcriptome in cattle.

    PubMed

    Nivet, Anne-Laure; Vigneault, Christian; Blondin, Patrick; Sirard, Marc-Andre

    2017-08-25

    In cows, the use of follicle-stimulating hormone (FSH) to stimulate follicular growth followed by a short period of FSH withdrawal has been shown to be beneficial for oocyte developmental competence. Although this treatment represents a useful optimization to generate highly competent oocytes, the underlying physiological process is not completely understood. The goal of this study was to investigate the role of luteinizing hormone (LH) action during FSH withdrawal before ovulation. To accomplish this, LH release was pharmacologically inhibited during the coasting period with gonadotropin-releasing hormone (GnRH) antagonists. Granulosa cells samples were obtained from cows stimulated with FSH during 3 days followed by a coasting period of 68 h and treated with a GnRH antagonist (cetrorelix group) or not (control). A significant reduction in the number of follicles at >10 mm diameter was observed with the cetrorelix group and gene expression of granulosa cells reveals that 747 transcripts are potentially regulated by LH. Further analysis indicates how the absence of LH may trigger early atresia, the upregulation of atretic agent as tumor protein P53 and transforming growth factor β1 and the inhibition of growth support. This work allows identification of genes that are associated with maintained follicular growth and conversely the ones leading to atresia in dominant pre-ovulatory follicles. © 2017 Japanese Society of Animal Science.

  9. Recombinant luteinizing hormone priming in multiple follicular stimulation for in-vitro fertilization in downregulated patients.

    PubMed

    Lisi, F; Caserta, D; Montanino, M; Berlinghieri, V; Bielli, W; Carfagna, P; Carra, M C; Costantino, A; Lisi, R; Poverini, R; Ciardo, F; Rago, R; Marci, R; Moscarini, M

    2012-09-01

    Follicle development is controlled amongst other factors by pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) that act in synergy in completing follicle maturation. Exogenous gonadotropins, combined with gonadotropin-releasing hormone agonists, have been successfully used in patients with ovulatory disorders undergoing assisted reproduction. There is some evidence of a beneficial role of androgens or LH administration before FSH stimulation. This study was designed to verify whether the addition of LH in the early follicular phase, in downregulated patients undergoing follicular stimulation for assisted reproduction, would add benefits in terms of general outcomes and pregnancy rates. We compared two groups of patients one of which was treated with recombinant FSH (rFSH) alone and the other with rFSH plus recombinant LH (rLH), in the early follicular phase only. The number of eggs recovered was higher in the group treated with FSH only; however, the number of embryos available at transfer was similar in the two groups and, more importantly, the number of Grades I and II embryos was higher in the group pretreated with LH. Similarly, although biochemical pregnancy rate and clinical pregnancy rates were similar in both groups, a beneficial role of LH priming was demonstrated by the higher implantation rate achieved in these patients.

  10. Sex-dependent endorphinergic and adrenergic control mechanisms of luteinizing hormone secretion in immature rats.

    PubMed

    Schulz, R; Wilhelm, A; Pirke, K M; Herz, A

    1985-06-01

    Previous studies in male and female immature rats have revealed striking sex differences as concerns endorphinergic and adrenergic control of luteinizing hormone (LH) secretion. The present study examines in 10 days old male and females rats whether these differences result from sexual differentiation of the brain, or acute effects of male and female gonadal hormones. The techniques employed to manipulate these mechanisms were gonadectomy immediately post-partum and androgenization. Androgenization on the 1st and 2nd day of life reduces the ability of naloxone to elevate serum LH levels in females, but failed to modify the LH-elevating effect of clonidine in males. Experiments with castrates showed that testosterone is critical for these sex-related differences. Treatment with testosterone on the 9th day of life of intact or gonadectomized rats revealed the ability of this hormone to modify LH-release acutely. We conclude that sexual differentiation of the brain may be of minor significance for the sex-related LH-control mechanisms in prepubertal rats. Of importance is the acute presence of testosterone, since in its absence male characteristics disappear.

  11. Evaluation of an immunoenzymometric assay (IEMA) using automated system for determination of luteinizing hormone and follicle stimulating hormone.

    PubMed

    Fonseca, E; Mason, M; Galván, R E; Pascoe, D; Ochoa, R; Hernández, M; Zárate, A

    1997-01-01

    It has been proposed that automated systems for immunoenzymometric assay (IEMA) may substitute traditional radioimmunoassay (RIA) for measurement of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in blood due to the advantage of being more rapid, higher sensitivity, lower cost and not requiring radioactive reagents. The study was designed to evaluate both systems using serum samples to determine luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations. The automatic system (ES-300) for IEMA utilized two monoclonal antibodies, one of them on the solid phase was the specific extractant for the antigen, and the other was a peroxidase labeled antibody which recognizes a different epitope in the antigen molecule, specifically bound in linear proportion to the antigen concentration. Blood samples were obtained from patients who were treated at the hospital for various clinical problems ("problem group") as well as blood samples from patients in whom FSH and LH concentrations were already known ("high", "medium" and "low" levels) by previous RIA ("control group"). IEMA showed a higher sensitivity, 0.42 and 0.96 mIU/ml for FSH and LH, respectively, whereas RIA was 1.95 mIU/ml for both hormones. Intra- and interassay coefficient of variation were below 10% within the range of 15-150 mIU/ml for FSH and 5-100 mIU/ml for LH; however, the coefficient of variation was 15-25% at lower concentrations of FSH and LH. Accuracy of IEMA was evaluated by recovery percentage, thus when high and medium concentrations of FSH and LH were analyzed the recovery was between 99-104%. On the other hand, the recovery was 110% when low levels of FSH and LH were used. In conclusion, IEMA resulted reliable when FSH and LH concentrations are in the middle and high range; likewise, the detection limit of IEMA was lower than RIA, particularly for FSH. On the bases of these results, IEMA showed several advantages over RIA, but its reliability diminishes when serum

  12. Immunoradiometric assay (IRMA) for human follicle stimulating hormone (FSH) and luteinizing hormone (LH) using common avidin solid phase.

    PubMed

    Vrinda, C; Paradkar, S N; Jyotsna, N; Sivaprasad, N

    2003-01-01

    This paper describes the use of avidin-biotin interaction as an affinity system, wherein avidin immobilized magnetizable particles (cellulose) are used as a common separation system in immunoradiometric assay (IRMA) for hormones of the human reproductive system, human follicle stimulating hormone (FSH), and luteinizing hormone (LH). Biotinylated probe was prepared by biotinylation of specific monoclonal antibody for respective antigen using the caproyl derivative of biotin N-hydroxysuccinimide. The detector antibody for the respective antigen was radiolabelled with 125I by a chloramine-T oxidation method and purified by gel filtration. In the IRMA procedure, standard/sample, respective biotinylated, and radiolabelled antibody as a single reagent, and avidin solid phase were added simultaneously to the assay tubes. After incubation for 3 h with shaking, the bound complex was quantitated for its radioactivity associated with the common avidin solid phase. Results showed that the developed assay protocol is applicable to IRMA of FSH and LH with good precision (intra and inter assay CV less than 8% and 11%, respectively), good assay range (0-200 mIU/mL) and analytical recovery (87-110%). The assay could detect 0.5 mIU/mL and 0.9 mIU/mL of FSH and LH, respectively, and showed good correlation with commercially available kits (FSH y = 0.98x + 0.21 and LH y = 0.99x + 0.18).

  13. Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors.

    PubMed Central

    Risma, K A; Clay, C M; Nett, T M; Wagner, T; Yun, J; Nilson, J H

    1995-01-01

    Hypersecretion of luteinizing hormone (LH) is implicated in infertility and miscarriages in women. A lack of animal models has limited progress in determining the mechanisms of LH toxicity. We have recently generated transgenic mice expressing a chimeric LH beta subunit (LH beta) in gonadotropes. The LH beta chimera contains the C-terminal peptide of the human chorionic gonadotropin beta subunit. Addition of this peptide to bovine LH beta resulted in a hormone with a longer half-life. Furthermore, targeted expression of the LH beta chimera led to elevated LH levels and infertility in female transgenics. These mice ovulated infrequently, maintained a prolonged luteal phase, and developed pathologic ovarian changes such as cyst formation, marked enlargement of ovaries, and granulosa cell tumors. Testosterone and estradiol levels were increased compared to nontransgenic littermates. An unusual extragonadal phenotype was also observed: transgenic females developed hydronephropathy and pyelonephritis. The pathology observed demonstrates a direct association between abnormal secretion of LH and infertility and underscores the utility of the transgenic model for studying how excess LH leads to cyst formation, ovarian tumorigenesis, and infertility. Images Fig. 2 Fig. 3 Fig. 5 PMID:7877975

  14. Hypersecretion of luteinizing hormone and ovarian steroids in women with recurrent early miscarriage.

    PubMed

    Watson, H; Kiddy, D S; Hamilton-Fairley, D; Scanlon, M J; Barnard, C; Collins, W P; Bonney, R C; Franks, S

    1993-06-01

    Polycystic ovary syndrome is associated with hypersecretion of luteinizing hormone (LH) which has been implicated in the aetiology of early pregnancy loss. Although 82% of women with recurrent early loss have polycystic ovaries on ultrasound imaging, random serum LH concentrations are normal. In the present study, we have obtained further information from serial samples concerning the cyclical patterns of gonadotrophin and sex steroid secretion in these women. Twenty-one women with recurrent early pregnancy loss and 10 multiparous controls were investigated; 81% of them and one of ten control subjects had polycystic ovaries. Mean mid-follicular and mid-luteal serum LH and follicle stimulating hormone (FSH) levels were similar in both groups. Seventeen women with pregnancy loss had either raised urinary LH excretion or a premature LH surge; one control subject had a premature LH surge. Total LH excretion during the cycle and mean follicular phase serum testosterone was significantly greater with early pregnancy loss than in the control group, the difference in LH being greatest in the early luteal phase. Urinary oestrone-3-glucuronide excretion was raised in the early luteal phase of the cycle in the group with early pregnancy loss; there was no difference between the groups in pregnanediol-3 alpha-glucuronide excretion. These data demonstrate abnormalities in LH secretion in 81% of women with recurrent fetal loss. Inappropriately raised LH levels may have adverse effects on the developing oocyte or endometrium either directly, or indirectly by causing an elevation in testosterone and oestrogen levels.

  15. Estradiol modulates the pulsatile secretion of biologically active luteinizing hormone in man.

    PubMed Central

    Veldhuis, J D; Dufau, M L

    1987-01-01

    We investigated the effects of estradiol on bioactive luteinizing hormone (LH) release in normal men using two complementary strategies: (i) steady state intravenous infusions of estradiol at its endogenous production rate, and (ii) oral administration of the antiestrogen, tamoxifen HCl. Immunoreactive and biologically active LH were monitored by radioimmunoassay and the rat interstitial cell testosterone bioassay, respectively. Estradiol infusions significantly suppressed mean plasma bioactive LH concentrations and decreased the bio/immuno LH ratio. Conversely, antiestrogen treatment enhanced spontaneous bioactive LH pulse frequency, increased bioactive LH pulse amplitude, and augmented plasma intrapulse and interpulse bio/immuno LH ratios. Low-dose pulsed injections of exogenous gonadotropin-releasing hormone (GnRH) also increased plasma bio/immuno LH ratios. However, tamoxifen attenuated the ability of exogenous GnRH to further enhance the bio/immuno LH ratio, which suggests that endogenous LH release was already maximally enriched in LH bioactivity during antiestrogen administration. We conclude that estradiol modulates the pulsatile secretion of LH molecules enriched in biological activity in man. PMID:3305575

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

    SciTech Connect

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

    1985-08-01

    The authors determined if luteinizing hormone (LH) synthesis is Ca2+ dependent and coupled to LH release. They monitored LH synthesis when LH release was stimulated either by specific (gonadotropin-releasing hormone (GnRH)) or nonspecific stimuli (50 mM K+ and 2 or 20 microM Ca2+ ionophore A23187) and inhibited by Ca2+-reduced medium. LH synthesis was estimated by measuring incorporation of (/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.

  17. Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome.

    PubMed

    Cadagan, David; Khan, Raheela; Amer, Saad

    2016-03-01

    This study examined whether a defect of steroid synthesis in ovarian theca cells may lead to the development of PCOS, through contributions to excess androgen secretion. Polycystic ovarian syndrome (PCOS) is one of the leading causes of infertility worldwide affecting around 1 in 10 of women of a reproductive age. One of the fundamental abnormalities in this syndrome is the presence of hormonal irregularities, including hyperandrogenemia, hyperinsulinemia and hypersecretion of luteinizing hormone (LH). Studies suggest that insulin treatment increases progesterone and androstenedione secretion in PCOS theca cells when compared to insulin treated normal theca cells. Furthermore the augmented effects of LH and insulin have been seen to increase ovarian androgen synthesis in non-PCOS theca cultures whilst also increasing the expression of steroidogenic enzymes specific to the PI3-K pathway. Our examination of primary thecal cultures showed an increase in both the expression of the steroidogenic enzyme CYP17 and androgen secretion in PCOS theca cells under basal conditions, when compared to non-PCOS cells. This was increased significantly under treatments of LH and insulin combined. Our results support the previous reported hypothesis that a dysfunction may exist within the PI3-K pathway. Specifically, that sensitivity exists to physiological symptoms including hyperinsulinemia and hyper secretion of LH found in PCOS through co-stimulation. The impact of these findings may allow the development of a therapeutic target in PCOS.

  18. Eurycoma longifolia extract increases intracellular production activity of luteinizing hormone (LH) in pituitary

    NASA Astrophysics Data System (ADS)

    Pratomo, H.

    2017-07-01

    Administration of the boiled water (extract) of Eurycoma longifolia (E. Longifolia) 18 mg/200 g body weight (bw) actually increases basophil cells in the anterior pituitary. Meanwhile, it is observed that basophil cells in anterior pituitary are producer cells of LH and FSH. Cell activity rate producing intracellular FSH does not increase in the amount significantly after administration of the E. longifolia onto the third day. The research attempts to prove the performance of E. longifolia to producer cells of luteinizing hormone (LH) in the anterior pituitary. Applied approach by a technical method of immunohistochemistry staining uses an antibody anti-LH. Observation is established to the treatment group of the E longifolia in a dose of 18 mg/200 g a bw on the 1st day and 3rd day, compared to control group of 1 ml distilled water on the 1st day and 3rd day. Research results that administration of the extract of E longifolia onto the third day has increased the activity of producer cells of LH in the pituitary, the synthesizing intracellular LH obviously. It can be concluded that E longifolia constitutes strong trigger in producer cells of LH to synthesize LH hormone.

  19. Plasma prolactin, thyroxine, triiodothyronine, testosterone, and luteinizing hormone during a photoinduced reproductive cycle in mallard drakes.

    PubMed

    Sharp, P J; Klandorf, H; McNeilly, A S

    1986-06-01

    The temporal relationships between plasma concentrations of prolactin, thyroxine (T4) and triiodothyronine (T3) were determined in a group of six wild mallard drakes during the development and maintenance of long-day refractoriness after transfer from 6 h light: 18 h darkness (6L:18D) to 20L:4D for 24 weeks. As shown by changes in the plasma concentrations of luteinizing hormone (LH) and testosterone, the birds came into breeding condition and then became long-day refractory within 5 weeks of photostimulation. Long-day refractoriness was maintained for the remainder of the study. Plasma prolactin began to increase immediately after photostimulation, although not as fast as the increases in plasma LH and testosterone. The concentration of plasma T4 also increased after photostimulation but, as shown by decreased plasma LH and testosterone levels, only after the birds had become long-day refractory. The development of long-day refractoriness was thus directly correlated with an increased plasma prolactin and not with a change in plasma concentration of T4. Plasma T3 decreased after photostimulation but returned to prestimulation values as the birds became long-day refractory and remained stable for the remainder of the study. Concentrations of plasma T4 and prolactin returned to baseline values after about 15 weeks photostimulation showing that the long-term maintenance of long-day refractoriness is not directly related to continuously high plasma concentrations of either hormone.

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

    PubMed Central

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

    1989-01-01

    The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10++ +]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells. PMID:2548207

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

    SciTech Connect

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

    1986-02-01

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

  2. Lack of effects of a lyposterolic extract of Serenoa repens on plasma levels of testosterone, follicle-stimulating hormone, and luteinizing hormone.

    PubMed

    Casarosa, C; Cosci di Coscio, M; Fratta, M

    1988-01-01

    Twenty men, aged 50 to 75 years (mean, 67 years), suffering from benign prostatic hypertrophy received 160 mg of a lyposterolic extract of Serenoa repens, twice daily for 30 days. Before and at the end of treatment, plasma levels of testosterone, follicle-stimulating hormone, and luteinizing hormone were determined. No changes in plasma hormone levels occurred as a result of treatment. It is concluded that Serenoa extract, which is useful in the treatment of benign prostatic hypertrophy, does not act via systemic changes of hormone levels.

  3. Acute Effect of Manganese on Hypothalamic Luteinizing Hormone Releasing Hormone Secretion in Adult Male Rats: Involvement of Specific Neurotransmitter Systems

    PubMed Central

    Prestifilippo, Juan Pablo; Fernández-Solari, Javier; De Laurentiis, Andrea; Mohn, Claudia Ester; de la Cal, Carolina; Reynoso, Roxana; Dees, W. Les; Rettori, Valeria

    2008-01-01

    Manganese chloride (MnCl2) is capable of stimulating luteinizing hormone releasing hormone (LHRH) secretion in adult male Sprague-Dawley rats through the activation of the hypothalamic nitric oxide/cyclic guanosine monophosphate (cGMP)/protein kinase G pathway. The present study aimed to determine the involvement of specific neurotransmitters involved in this action. Our results indicate that dopamine, but not glutamic acid and prostaglandinds, mediates the MnCl2 stimulated secretion of LHRH from medial basal hypothalami in vitro, as well as increases the activity of nitric oxide synthase. Furthermore, a biphasic response was observed in that gamma aminobutyric acid (GABA) release was also increased, which acts to attenuate the MnCl2 action to stimulate LHRH secretion. Although it is clear that manganese (Mn+2) can acutely induce LHRH secretion in adult males, we suggest that the additional action of MnCl2 to release GABA, a LHRH inhibitor, may ultimately contribute to suppressed reproductive function observed in adult animals following exposure to high chromic levels of Mn+2. PMID:18603625

  4. Distribution of luteinizing hormone-releasing hormone in the upper brainstem and diencephalon of the cat: an immunocytochemical study.

    PubMed

    Belda, M; Coveñas, R; Narváez, J A; Aguirre, J A; Tramu, G

    2000-03-01

    The distribution of luteinizing hormone-releasing hormone (LH-RH)-immunostained cell bodies and fibres was studied in the brainstem and diencephalon of the cat using an indirect immunoperoxidase technique. The brainstem and the thalamus were devoid of immunostained cell bodies, whereas in the hypothalamus immunopositive perikarya were observed in the supraoptic nucleus, the anterior hypothalamus, the preoptic region and in the arcuate nucleus. Our findings also showed that the hypothalamus is richer in immunostained fibres, and that in this region such fibres are more widely distributed than in the thalamus and upper brainstem. No immunopositive fibres were observed in the lower brainstem. Our results point to a more widespread distribution of LH-RH-immunostained perikarya in the cat hypothalamus than that previously reported in the cat; a similar distribution to that found in the rat, and a more restricted distribution than in primates. Additionally, our study shows a more widespread distribution of immunostained fibres in the cat brainstem and diencephalon than that previously described for other mammals. In this context, our results describe for the first time in the mammals central nervous system fibres containing LH-RH located in the stria medullaris of the thalamus, the supramammillary decussation, the laterodorsal and lateroposterior thalamic nuclei, the nucleus reuniens, the supraoptic nucleus, and the optic chiasm. Thus, our findings reveal that LH-RH-immunostained structures are widely distributed in the upper brainstem and in the diencephalon of the cat, suggesting that the peptide may be involved in several physiological functions.

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

    SciTech Connect

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

    1995-03-01

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

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

    PubMed

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

    2011-01-01

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

  7. Targeted chemotherapy of endometrial, ovarian and breast cancers with cytotoxic analogs of luteinizing hormone-releasing hormone (LHRH).

    PubMed

    Engel, J B; Schally, A V; Buchholz, S; Seitz, S; Emons, G; Ortmann, O

    2012-08-01

    Receptors luteinizing hormone-releasing hormone (LHRH) are expressed in about 80 % of human endometrial and ovarian cancers and account for more than 50 % of breast cancers including triple negative breast cancers. Apart from the pituitary and reproductive organs, no other organs or hematopoietic stem cells express LHRH (GnRH) receptors. Thus, these receptors can be regarded as an ideal target for a personalized medicine approach in cancer therapy. AEZS-108 (formerly known as AN-152) in which doxorubin is linked to the LHRH agonist [D: -Lys(6)]LHRH, appears to be the most advanced compound in late stage clinical development. Results of phase I and phase II clinical trials in patients with gynecological cancers demonstrated anticancer activity without any cardiotoxicity even in highly pretreated patients. AEZS-108 is therefore being considered for phase II trials in triple negative breast cancers and phase III studies in advanced endometrial cancers positive for LHRH-receptor. EP-100 is a membrane-disrupting peptide targeted to LHRH receptors, which is undergoing early clinical studies in ovarian cancer patients.

  8. Germ-line activation of the luteinizing hormone receptor directly drives spermiogenesis in a nonmammalian vertebrate

    PubMed Central

    Chauvigné, François; Zapater, Cinta; Gasol, Josep M.; Cerdà, Joan

    2014-01-01

    In both mammals and teleosts, the differentiation of postmeiotic spermatids to spermatozoa (spermiogenesis) is thought to be indirectly controlled by the luteinizing hormone (LH) acting through the LH/choriogonadotropin receptor (LHCGR) to stimulate androgen secretion in the interstitial Leydig cells. However, a more direct, nonsteroidal role of LH mediating the spermiogenic pathway remains unclear. Using a flatfish with semicystic spermatogenesis, in which spermatids are released into the seminiferous lobule lumen (SLL), where they develop into spermatozoa without direct contact with the supporting Sertoli cells, we show that haploid spermatids express the homolog of the tetrapod LHCGR (Lhcgrba). Both native Lh and intramuscularly injected His-tagged recombinant Lh (rLh) are immunodetected bound to the Lhcgrba of free spermatids in the SLL, showing that circulating gonadotropin can reach the intratubular compartment. In vitro incubation of flatfish spermatids isolated from the SLL with rLh specifically promotes their differentiation into spermatozoa, whereas recombinant follicle-stimulating hormone and steroid hormones are ineffective. Using a repertoire of molecular markers and inhibitors, we find that the Lh-Lhcgrba induction of spermiogenesis is mediated through a cAMP/PKA signaling pathway that initiates the transcription of genes potentially involved in the function of spermatozoa. We further show that Lhcgrba expression in germ cells also occurs in distantly related fishes, suggesting this feature is likely conserved in teleosts regardless of the type of germ cell development. These data reveal a role of LH in vertebrate germ cells, whereby a Lhcgrba-activated signaling cascade in haploid spermatids directs gene expression and the progression of spermiogenesis. PMID:24474769

  9. Germ-line activation of the luteinizing hormone receptor directly drives spermiogenesis in a nonmammalian vertebrate.

    PubMed

    Chauvigné, François; Zapater, Cinta; Gasol, Josep M; Cerdà, Joan

    2014-01-28

    In both mammals and teleosts, the differentiation of postmeiotic spermatids to spermatozoa (spermiogenesis) is thought to be indirectly controlled by the luteinizing hormone (LH) acting through the LH/choriogonadotropin receptor (LHCGR) to stimulate androgen secretion in the interstitial Leydig cells. However, a more direct, nonsteroidal role of LH mediating the spermiogenic pathway remains unclear. Using a flatfish with semicystic spermatogenesis, in which spermatids are released into the seminiferous lobule lumen (SLL), where they develop into spermatozoa without direct contact with the supporting Sertoli cells, we show that haploid spermatids express the homolog of the tetrapod LHCGR (Lhcgrba). Both native Lh and intramuscularly injected His-tagged recombinant Lh (rLh) are immunodetected bound to the Lhcgrba of free spermatids in the SLL, showing that circulating gonadotropin can reach the intratubular compartment. In vitro incubation of flatfish spermatids isolated from the SLL with rLh specifically promotes their differentiation into spermatozoa, whereas recombinant follicle-stimulating hormone and steroid hormones are ineffective. Using a repertoire of molecular markers and inhibitors, we find that the Lh-Lhcgrba induction of spermiogenesis is mediated through a cAMP/PKA signaling pathway that initiates the transcription of genes potentially involved in the function of spermatozoa. We further show that Lhcgrba expression in germ cells also occurs in distantly related fishes, suggesting this feature is likely conserved in teleosts regardless of the type of germ cell development. These data reveal a role of LH in vertebrate germ cells, whereby a Lhcgrba-activated signaling cascade in haploid spermatids directs gene expression and the progression of spermiogenesis.

  10. Involvement of Luteinizing Hormone in Alzheimer Disease Development in Elderly Women.

    PubMed

    Rao, C V

    2017-03-01

    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.

  11. FOXO1 Transcription Factor Inhibits Luteinizing Hormone β Gene Expression in Pituitary Gonadotrope Cells*

    PubMed Central

    Arriola, David J.; Mayo, Susan L.; Skarra, Danalea V.; Benson, Courtney A.; Thackray, Varykina G.

    2012-01-01

    Synthesis of luteinizing hormone (LH) is tightly controlled by a complex network of hormonal signaling pathways that can be modulated by metabolic cues, such as insulin. One group of candidate genes that may be regulated by insulin signaling in pituitary gonadotrope cells is the FOXO subfamily of forkhead transcription factors. In this study we investigated whether FOXO1 is expressed in gonadotropes and if it can modulate LH β-subunit (Lhb) gene expression. We demonstrated that FOXO1 is expressed in murine gonadotrope cells and that insulin signaling increased FOXO1 phosphorylation and cytoplasmic localization in a PI3K-dependent manner. We also showed that FOXO1 repressed basal transcription and gonadotropin-releasing hormone (GnRH) induction of both the murine and human LHB genes in LβT2 cells, suggesting that FOXO1 regulation of LHB transcription may be conserved between rodents and humans. Although we did not detect FOXO1 binding to the proximal Lhb promoter, the FOXO1 DNA binding domain was necessary for the suppression, suggesting that FOXO1 exerts its effect through protein-protein interactions with transcription factors/cofactors required for Lhb gene expression. FOXO1 repression mapped to the proximal Lhb promoter containing steroidogenic factor 1 (SF1), pituitary homeobox 1 (PTX1), and early growth response protein 1 (EGR1) binding elements. Additionally, FOXO1 blocked induction of the Lhb promoter with overexpressed SF1, PTX1, and EGR1, indicating that FOXO1 repression occurs via these transcription factors but not through regulation of their promoters. In summary, we demonstrate that FOXO1 phosphorylation and cellular localization is regulated by insulin signaling in gonadotropes and that FOXO1 inhibits Lhb transcription. Our study also suggests that FOXO1 may play an important role in controlling LH levels in response to metabolic cues. PMID:22865884

  12. FOXO1 transcription factor inhibits luteinizing hormone β gene expression in pituitary gonadotrope cells.

    PubMed

    Arriola, David J; Mayo, Susan L; Skarra, Danalea V; Benson, Courtney A; Thackray, Varykina G

    2012-09-28

    Synthesis of luteinizing hormone (LH) is tightly controlled by a complex network of hormonal signaling pathways that can be modulated by metabolic cues, such as insulin. One group of candidate genes that may be regulated by insulin signaling in pituitary gonadotrope cells is the FOXO subfamily of forkhead transcription factors. In this study we investigated whether FOXO1 is expressed in gonadotropes and if it can modulate LH β-subunit (Lhb) gene expression. We demonstrated that FOXO1 is expressed in murine gonadotrope cells and that insulin signaling increased FOXO1 phosphorylation and cytoplasmic localization in a PI3K-dependent manner. We also showed that FOXO1 repressed basal transcription and gonadotropin-releasing hormone (GnRH) induction of both the murine and human LHB genes in LβT2 cells, suggesting that FOXO1 regulation of LHB transcription may be conserved between rodents and humans. Although we did not detect FOXO1 binding to the proximal Lhb promoter, the FOXO1 DNA binding domain was necessary for the suppression, suggesting that FOXO1 exerts its effect through protein-protein interactions with transcription factors/cofactors required for Lhb gene expression. FOXO1 repression mapped to the proximal Lhb promoter containing steroidogenic factor 1 (SF1), pituitary homeobox 1 (PTX1), and early growth response protein 1 (EGR1) binding elements. Additionally, FOXO1 blocked induction of the Lhb promoter with overexpressed SF1, PTX1, and EGR1, indicating that FOXO1 repression occurs via these transcription factors but not through regulation of their promoters. In summary, we demonstrate that FOXO1 phosphorylation and cellular localization is regulated by insulin signaling in gonadotropes and that FOXO1 inhibits Lhb transcription. Our study also suggests that FOXO1 may play an important role in controlling LH levels in response to metabolic cues.

  13. Interaction Between Luteinizing Hormone-Releasing Hormone and GM1-Doped Cholesterol/Sphingomyelin Vesicles: A Spectroscopic Study.

    PubMed

    Shahzadi, Zarrin; Mukhopadhyay, Chaitali

    2017-09-11

    Understanding the role of neural membrane in translocation and action of neurohormone is of great importance. Luteinizing hormone-releasing hormone (LHRH) is a neuropeptide hormone and it acts as a final signaling molecule by stimulating the synthesis of LH and FSH to maintain reproduction in all vertebrates. The receptors of LHRH are found in breast tumors and pituitary gland in the brain. Moreover, neural plasma membrane is also found to contain specific binding site for LHRH. The mechanism by which LHRH binds to membrane before it binds to the receptors is a very critical step and can have a profound impact upon the translation of peptide across the membrane. A complex form of glycosphingolipids known as Ganglioside is an important component of plasma membrane of nerve cells and breast tumor tissues. They play an important role in various physiological membrane processes. Therefore, the interaction of ganglioside-containing membrane with LHRH might be crucial in aiding the LHRH to translate through the neural membrane and reach its receptor for binding and activation. Using CD, UV-Absorbance, and fluorescence spectroscopy, the effect of Ganglioside Monosialo 1(GM1)-induced conformational changes of LHRH in the presence of Cholesterol (CHOL)/Sphingomyelin (SM) and GM1/CHOL/SM vesicles was studied. The aforesaid spectroscopic studies show that LHRH is able to bind with both the vesicles, but GM1-containing vesicles interact more effectively than vesicles without GM1. CHOL/SM vesicles partially disturb the conformation of the peptide. Moreover, binding of LHRH to GM1/CHOL/SM vesicles induces loss of conformational rigidity and attainment of a random coil.

  14. Effects of external radiation therapy for cancer of the prostate on the serum concentrations of testosterone, follicle-stimulating hormone, luteinizing hormone and prolactin

    SciTech Connect

    Tomic, R.; Bergman, B.; Damber, J.E.; Littbrand, B.; Loefroth, P.O.

    1983-08-01

    Testosterone, luteinizing hormone, follicle-stimulating hormone and prolactin were analyzed in serum from 31 patients with carcinoma of the prostate treated primarily with megavoltage radiation therapy. The total tumor dose varied between 58 and 71 gray (mean 63.5 gray). Absorbed doses to the testes were measured at approximately 1 to more than 10 gray. We investigated retrospectively 17 patients 3 to 60 months (mean 20 months) after therapy and found significantly lower serum testosterone concentrations and significantly higher luteinizing and follicle-stimulating hormone concentrations than in age-matched controls. Of the patients, 14 were followed before and after radiation treatment. Testosterone concentrations were reduced significantly 1 week as well as 3 months after treatment but pre-treatment values were found on analysis 6 and 12 months after treatment. The values for luteinizing and follicle-stimulating hormones were significantly higher 3, 6 and 12 months after radiation treatment compared to pre-treatment values. The follicle-stimulating hormone value already increased after 1 week. The greatest observed testosterone alteration occurred 1 week after treatment in patients who received more than 10 gray over the gonads. The use of lead shields protecting the testes reduced the dose absorbed to the gonads by approximately 50 percent.

  15. Expression of luteinizing hormone/chorionic gonadotropin receptor in the rat pineal gland.

    PubMed

    Itoh, Masanori T; Hosaka, Takeshi; Takahashi, Noriyuki; Ishizuka, Bunpei

    2006-08-01

    Luteinizing hormone (LH) influences the secretion of melatonin (N-acetyl-5-methoxytryptamine) from the pineal gland. The present study examined the possible presence of LH/chorionic gonadotropin (CG) receptor in the pineal gland of adult female rats. Reverse transcriptase-polymerase chain reaction analyses demonstrated that LH/CG receptor mRNA is expressed in the pineal gland. Western blotting showed that the pineal gland, like the ovary, contains an 80 kDa receptor protein. Immunohistochemistry revealed that LH/CG receptor, arylalkylamine N-acetyltransferase (a regulatory enzyme in melatonin biosynthesis) and serotonin (a melatonin precursor) are localized primarily to the same cells of the pineal gland. We further found that the levels of pineal LH/CG receptor protein in normal cycling female rats change significantly during the estrous cycle, being lowest at early metestrus. These results demonstrate that LH/CG receptor is expressed in the pineal gland, primarily in melatonin-synthesizing cells, namely pinealocytes. Furthermore, it is suggested that LH influences pineal melatonin secretion through binding to this receptor. In addition, LH/CG receptor levels in the pineal gland are regulated during the estrous cycle under normal physiological conditions.

  16. BMP-6 modulates somatostatin effects on luteinizing hormone production by gonadrotrope cells.

    PubMed

    Toma, Kishio; Otsuka, Fumio; Oguni, Kohei; Terasaka, Tomohiro; Komatsubara, Motoshi; Tsukamoto-Yamauchi, Naoko; Inagaki, Kenichi; Makino, Hirofumi

    2016-02-01

    The effects of somatostatin analogs and roles of BMP-6 in the regulation of luteinizing hormone (LH) secretion were investigated using mouse gonadotrope LβT2 cells. LH mRNA expression and LH secretion induced by GnRH were suppressed by treatments with somatostatin analogs, including octreotide and pasireotide, in LβT2 cells. Of note, the inhibitory effects of somatostatin analogs on LH secretion were enhanced by the action of BMP-6. BMP-6 increased the expression levels of somatostatin receptor (SSTR)5, suggesting that BMP-6 upregulates SSTR activity that leads to reduction of GnRH-induced LH secretion. In addition, GnRH-induced phosphorylation of MAPKs including ERK, but not P38 or SAPK, was suppressed by pasireotide in the presence of BMP-6. Given that each inhibitor of ERK, JNK or P38 signaling suppressed GnRH-induced LH transcription, MAPKs are individually involved in the induction of LH production by LβT2 cells. Somatostatin analogs also impaired BMP-6-induced Smad1/5/8 phosphorylation by suppressing BMPRs and augmenting Smad6/7 expression. Collectively, the results indicate that somatostatin analogs have dual effects on the modulation of GnRH-induced MAPK signaling and BMP activity. The pituitary BMP system may play a regulatory role in GnRH-induced LH secretion by tuning the responsiveness to somatostatin analogs in gonadotrope cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Cortisol interferes with the estradiol-induced surge of luteinizing hormone in the ewe.

    PubMed

    Wagenmaker, Elizabeth R; Breen, Kellie M; Oakley, Amy E; Pierce, Bree N; Tilbrook, Alan J; Turner, Anne I; Karsch, Fred J

    2009-03-01

    Two experiments were conducted to test the hypothesis that cortisol interferes with the positive feedback action of estradiol that induces the luteinizing hormone (LH) surge. Ovariectomized sheep were treated sequentially with progesterone and estradiol to create artificial estrous cycles. Cortisol or vehicle (saline) was infused from 2 h before the estradiol stimulus through the time of the anticipated LH surge in the artificial follicular phase of two successive cycles. The plasma cortisol increment produced by infusion was approximately 1.5 times greater than maximal concentrations seen during infusion of endotoxin, which is a model of immune/inflammatory stress. In experiment 1, half of the ewes received vehicle in the first cycle and cortisol in the second; the others were treated in reverse order. All ewes responded with an LH surge. Cortisol delayed the LH surge and reduced its amplitude, but both effects were observed only in the second cycle. Experiment 2 was modified to provide better control for a cycle effect. Four treatment sequences were tested (cycle 1-cycle 2): vehicle-vehicle, cortisol-cortisol, vehicle-cortisol, cortisol-vehicle. Again, cortisol delayed but did not block the LH surge, and this delay occurred in both cycles. Thus, an elevation in plasma cortisol can interfere with the positive feedback action of estradiol by delaying and attenuating the LH surge.

  18. Elevated luteinizing hormone induces expression of its receptor and promotes steroidogenesis in the adrenal cortex

    PubMed Central

    Kero, Jukka; Poutanen, Matti; Zhang, Fu-Ping; Rahman, Nafis; McNicol, Anne Marie; Nilson, John H.; Keri, Ruth A.; Huhtaniemi, Ilpo T.

    2000-01-01

    Transgenic (TG) female mice expressing bLHβ-CTP (a chimeric protein derived from the β-subunit of bovine luteinizing hormone [LH] and a fragment of the β-subunit of human chorionic gonadotropin [hCG]) exhibit elevated serum LH, infertility, polycystic ovaries, and ovarian tumors. In humans, increased LH secretion also occurs in infertility and polycystic ovarian syndrome, often concomitant with adrenocortical dysfunction. We therefore investigated adrenal function in LH overexpressing bLHβ-CTP female mice. The size of their adrenals was increased by 80% with histological signs of cortical stimulation. Furthermore, adrenal steroid production was increased, with up to 14-fold elevated serum corticosterone. Primary adrenal cells from TG and control females responded similarly to ACTH stimulation, but, surprisingly, the TG adrenals responded to hCG with significantly increased cAMP, progesterone, and corticosterone production. LH receptor (LHR) expression and activity were also elevated in adrenals from female TG mice, but gonadectomized TG females showed no increase in corticosterone, suggesting that the dysfunctional ovaries of the intact TG females promote adrenocortical hyperfunction. We suggest that, in intact TG females, enhanced ovarian estrogen synthesis causes increased secretion of prolactin (PRL), which elevates LHR expression. Chronically elevated serum LH, augmented by enhanced PRL production, induces functional LHR expression in mouse adrenal cortex, leading to elevated, LH-dependent, corticosterone production. Thus, besides polycystic ovaries, the bLHβ-CTP mice provide a useful model for studying human disorders related to elevated LH secretion and adrenocortical hyperfunction. PMID:10712435

  19. Elevated luteinizing hormone induces expression of its receptor and promotes steroidogenesis in the adrenal cortex.

    PubMed

    Kero, J; Poutanen, M; Zhang, F P; Rahman, N; McNicol, A M; Nilson, J H; Keri, R A; Huhtaniemi, I T

    2000-03-01

    Transgenic (TG) female mice expressing bLHbeta-CTP (a chimeric protein derived from the beta-subunit of bovine luteinizing hormone [LH] and a fragment of the beta-subunit of human chorionic gonadotropin [hCG]) exhibit elevated serum LH, infertility, polycystic ovaries, and ovarian tumors. In humans, increased LH secretion also occurs in infertility and polycystic ovarian syndrome, often concomitant with adrenocortical dysfunction. We therefore investigated adrenal function in LH overexpressing bLHbeta-CTP female mice. The size of their adrenals was increased by 80% with histological signs of cortical stimulation. Furthermore, adrenal steroid production was increased, with up to 14-fold elevated serum corticosterone. Primary adrenal cells from TG and control females responded similarly to ACTH stimulation, but, surprisingly, the TG adrenals responded to hCG with significantly increased cAMP, progesterone, and corticosterone production. LH receptor (LHR) expression and activity were also elevated in adrenals from female TG mice, but gonadectomized TG females showed no increase in corticosterone, suggesting that the dysfunctional ovaries of the intact TG females promote adrenocortical hyperfunction. We suggest that, in intact TG females, enhanced ovarian estrogen synthesis causes increased secretion of prolactin (PRL), which elevates LHR expression. Chronically elevated serum LH, augmented by enhanced PRL production, induces functional LHR expression in mouse adrenal cortex, leading to elevated, LH-dependent, corticosterone production. Thus, besides polycystic ovaries, the bLHbeta-CTP mice provide a useful model for studying human disorders related to elevated LH secretion and adrenocortical hyperfunction.

  20. Changes in luteinizing hormone secretion after estradiol treatment in prepubertal Nelore heifers

    PubMed Central

    Cardoso, Daniel; Guerra, Fábio F.; Peiró, Juliana R.; Perri, Silvia H.V.; Nogueira, Guilherme P.

    2011-01-01

    Changes in luteinizing hormone (LH) secretion after 17β-estradiol (E2) injection were evaluated during sexual maturation in 10 prepubertal Nelore heifers. Heifers were divided into 2 groups: intact (I) and ovariectomized (OVX). 17β-estradiol (2 μg/kg) was administered to both groups at 10, 13, and 17 mo of age. Only at 10 mo of age was there a greater mean LH concentration in OVX heifers (1.33 ± 0.29 ng/mL) compared with the I group (0.57 ± 0.15 ng/mL). At 13 and 17 mo of age there was no significant difference between the 2 groups in any of the evaluated variables (number of peaks, total peak area, greatest peak area, and time to greatest peak occurrence). This suggests a decrease in negative E2 feedback associated with an increase in positive feedback to LH secretion during sexual maturation, and these were likely the key factors that determined the time of first ovulation in Nelore heifers. PMID:22211002

  1. Reevaluation of the relative activities of the pituitary glycoprotein hormones (follicle-stimulating hormone, luteinizing hormone, and thyrotrophin) from the green sea turtle, Chelonia mydas.

    PubMed

    Licht, P; Papkoff, H

    1985-06-01

    The discovery that the follicle-stimulating hormone (FSH) previously prepared from the green sea turtle, Chelonia mydas, contained a major neurohypophysial contaminant prompted a repurification and characterization of the glycoprotein hormones in this turtle. Results reaffirmed the physicochemical distinctiveness of the three hormones. Minimal cross-contamination between hormones (less than 2%) was achieved by ion-exchange chromatography, subunit dissociation (of contaminating luteinizing hormone (LH], gel filtration, and immuno-affinity chromatography. New preparations of FSH and thyrotrophin (TSH) derived from adult pituitaries proved to be more potent than those described previously (the degree depending on the nature of the assay); FSH showed the expected increase in activity based on estimated contamination of previous preparations. LH was similar to original preparations except for enhanced activity in FSH radioreceptor assays. Binding assays (in heterologous and homologous systems) again demonstrated the general absence of an FSH-specific receptor in the reptilian (chelonian and squamate) testes. In an in vivo bioassay in the lizard Anolis, the turtle FSH was orders of magnitude more potent than LH in stimulating both testis growth and androgen secretion, but in vitro LH was considerably more potent than FSH in stimulating androgen secretion in squamate and chelonian testes. Thus, the possibility exists that androgen secretion in some chelonian systems may exhibit a high degree of LH specificity like that of mammals and birds.

  2. Effect of supplemental light on growth, prolactin, progesterone and luteinizing hormone in water buffalo ( Bubalus bubalis)

    NASA Astrophysics Data System (ADS)

    Perera, K. S.; Gwazdauskas, F. C.; Akers, R. M.; McGilliard, M. L.

    1989-06-01

    Fifty non-pregnant Surti buffalo heifers aged between 17 and 42 months ( n=24, <24 months; n=26, >24 months) were randomly assigned to groups subject to either natural daylight +4h supplemental light ( n=25) or natural day light ( n=25), to study changes in growth, serum prolactin (Prl), progesterone (P4) and luteinizing hormone (LH) to supplemental lighting. Ambient temperatures (T) and relative humidity (RH) generally were >27° C and <70% during the day-time, respectively. Light-supplemented heifers had 16.2 kg net body weight (BW) gain at 9 weeks compared to 20.8 kg for controls, but higher mean Prl after 6.5 weeks ( P<0.01), and higher P4 (0.41 vs 0.19 ng/ml; P<0.06) than control heifers. Older heifers had 39.7% greater BW ( P<0.01), but a net 4.3% BW gain compared to a 10.1% gain for younger heifers at 10 weeks. Older, light-supplemented heifers had higher mean P4 (0.63 vs 0.19 ng/ml; P<0.07) than the other groups. These weight and hormonal changes suggest that 4 h supplemental light can alter growth and endocrine function in buffaloes under similar planes of nutrition. While light supplementation did not have a positive effect on body wieght during the 10 week study, body weight and endocrine changes due to supplemental light may be important factors for initiation of reproductive cyclicity.

  3. Uncoupling clutch size, prolactin, and luteinizing hormone using experimental egg removal.

    PubMed

    Ryan, Calen P; Dawson, Alistair; Sharp, Peter J; Williams, Tony D

    2015-03-01

    Clutch size is a key avian fitness and life history trait. A physiological model for clutch size determination (CSD), involving an anti-gonadal effect of prolactin (PRL) via suppression of luteinizing hormone (LH), was proposed over 20 years ago, but has received scant experimental attention since. The few studies looking at a PRL-based mechanistic hypothesis for CSD have been equivocal, but recent experiments utilizing a pharmacological agent to manipulate PRL in the zebra finch (Taeniopygia guttata) found no support for a role of this hormone in clutch size determination. Here, we take a complementary approach by manipulating clutch size through egg removal, examining co-variation in PRL and LH between two breeding attempts, as well as through experimentally-extended laying. Clutch size increased for egg removal females, but not controls, but this was not correlated with changes in PRL or LH. There were also no differences in PRL between egg removal females and controls, nor did PRL levels during early, mid- or late-laying of supra-normal clutches predict clutch size. By uncoupling PRL, LH and clutch size in our study, several key predictions of the PRL-based mechanistic model for CSD were not supported. However, a positive correlation between PRL levels late in laying and days relative to the last egg (clutch completion) provides an alternative explanation for the equivocal results surrounding the conventional PRL-based physiological model for CSD. We suggest that females coordinate PRL-mediated incubation onset with clutch completion to minimize hatching asynchrony and sibling hierarchy, a behavior that is amplified in females laying larger clutches.

  4. Selective optogenetic activation of arcuate kisspeptin neurons generates pulsatile luteinizing hormone secretion

    PubMed Central

    Han, Su Young; McLennan, Timothy; Czieselsky, Katja; Herbison, Allan E.

    2015-01-01

    Normal reproductive functioning in mammals depends upon gonadotropin-releasing hormone (GnRH) neurons generating a pulsatile pattern of gonadotropin secretion. The neural mechanism underlying the episodic release of GnRH is not known, although recent studies have suggested that the kisspeptin neurons located in the arcuate nucleus (ARN) may be involved. In the present experiments we expressed channelrhodopsin (ChR2) in the ARN kisspeptin population to test directly whether synchronous activation of these neurons would generate pulsatile luteinizing hormone (LH) secretion in vivo. Characterization studies showed that this strategy targeted ChR2 to 70% of all ARN kisspeptin neurons and that, in vitro, these neurons were activated by 473-nm blue light with high fidelity up to 30 Hz. In vivo, the optogenetic activation of ARN kisspeptin neurons at 10 and 20 Hz evoked high amplitude, pulse-like increments in LH secretion in anesthetized male mice. Stimulation at 10 Hz for 2 min was sufficient to generate repetitive LH pulses. In diestrous female mice, only 20-Hz activation generated significant increments in LH secretion. In ovariectomized mice, 5-, 10-, and 20-Hz activation of ARN kisspeptin neurons were all found to evoke LH pulses. Part of the sex difference, but not the gonadal steroid dependence, resulted from differential pituitary sensitivity to GnRH. Experiments in kisspeptin receptor-null mice, showed that kisspeptin was the critical neuropeptide underlying the ability of ARN kisspeptin neurons to generate LH pulses. Together these data demonstrate that synchronized activation of the ARN kisspeptin neuronal population generates pulses of LH. PMID:26443858

  5. Could bone tissue be a target for luteinizing hormone/chorionic gonadotropin?

    PubMed

    Mansell, Jason P; Bailey, Allen J; Yarram, Sarah J

    2007-04-15

    Ovariectomy (OVX) and Zoladex administration to adult rats gave conflicting results with respect to the excretion of total urinary hydroxyproline (OH-Pro), a valuable indicator of bone collagen catabolism. Whereas OVX culminated in early (1 week) increases in OH-Pro, the use of Zoladex actually lowered OH-Pro and showed no sign of increasing over controls for a 2-month period. Since both OVX and Zoladex produce a state of estrogen deficiency we reasoned that the differential effects of the two procedures on OH-Pro were attributed to LH status. Receptors for luteinizing hormone (LH)/human chorionic gonadotropin (hCG) have been identified in many, non-gonadal, estrogen sensitive sites and although bone is receptive to estrogen what effects LH/hCG might have upon bone metabolism have received scant attention. Treatment of osteoblasts in culture with a urinary derived formulation of hCG resulted in increased alkaline phosphatase (ALP) activity, raised matrix mettaloproteinase-2 (MMP-2) levels and increased expression of type I collagen. Further studies, using murine calvaria, supported a bone-resorbing effect of hCG. Taken together our initial findings suggested that raised hCG and/or LH might lead to an overall increase in bone matrix turnover as reported for puberty, pregnancy and the menopause. However, when the urinary derived preparation of hCG was replaced with recombinant hormone no changes in osteoblast activity were found implying the presence of contaminating agents in the urine derived hCG. Herein we describe that epidermal growth factor (EGF) could account for the changes observed for urinary derived hCG in osteoblast cultures and that the effects of LH/hCG on bone tissue are probably indirect.

  6. Effect of interferon-gamma treatment on 24-hour variations in plasma ACTH, growth hormone, prolactin, luteinizing hormone and follicle-stimulating hormone of male rats.

    PubMed

    Cano, Pilar; Cardinali, Daniel P; Jimenez, Vanessa; Alvarez, Maria P; Cutrera, Rodolfo A; Esquifino, Ana I

    2005-01-01

    Interferon-gamma (IFN-gamma) is a cytokine produced by T helper cells on antigenic challenge that may affect the release of several pituitary hormones. However, in vitro or in vivo studies have yielded disparate results with stimulatory, inhibitory or absent effects of IFN on pituitary hormone release. One of the reasons for these discrepancies could be that hormone changes were commonly assessed at a single time point in the day-night cycle. In this study we measured the circadian pattern of plasma ACTH, growth hormone (GH), prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) at 6 different time points within a 24-hour cycle in adult male Wistar rats. Groups of 6-8 rats kept under light from 08:00 to 20:00 h daily received 5 daily injections intraperitoneally of human IFN-gamma (10(5) IU/kg body weight) or saline at 08:30 h. Plasma ACTH, GH, prolactin, LH and FSH levels were measured by a homologous specific double antibody RIA. A factorial ANOVA for main effects indicated a significant 43% increase of circulating prolactin in IFN-gamma-treated rats. Time of day changes were significant for the five hormones examined and these diurnal variations became altered by IFN-gamma administration, with a phase advance of ACTH peak, a suppression of the rest phase peak of GH, the appearance of a second peak of prolactin at an early phase of daily photoperiod, and the blunting of the 24-hour variations of plasma FSH. The data point out an effect of IFN-gamma on the mechanisms responsible for the circadian organization of pituitary hormone release. Copyright (c) 2005 S. Karger AG, Basel.

  7. Is there a need for recombinant human luteinizing hormone (lutropin alfa) supplementation in ovarian stimulation for assisted reproduction?

    PubMed

    Nawroth, Frank; Ludwig, Michael

    2006-05-01

    Luteinizing hormone is now available as the recombinant product, lutropin alfa for the treatment of female infertility. It is necessary in the natural process of follicular growth and maturation. It is not yet clear which patients really benefit from the addition of this medication to conventional gonadotropin stimulation procedures in infertility treatment. Certainly, it has a proven benefit in patients suffering from hypogonadotropic hypogonadism (WHO I). Others may be older patients, patients with a profound gonadotropin suppression stimulated in long gonadotropin-releasing hormone agonist protocols, or patients with poor ovarian response to conventional stimulation strategies. The available data are reviewed herein.

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

    PubMed

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

    2003-12-01

    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 (<1.2 ng/mL or > 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.

  9. Treatment of nitrosamine-induced pancreatic tumors in hamsters with analogs of somatostatin and luteinizing hormone-releasing hormone

    SciTech Connect

    Paz-Bouza, J.I.; Redding, T.W.; Schally, A.V.

    1987-02-01

    Pancreatic ductal adenocarcinoma was induced in female Syrian golden hamsters by injecting N-nitrosobis(2-oxopropyl)amine (BOP) once a week at a dose of 10 mg per kg of body weight for 18 weeks. Hamsters were then treated with somatostatin analog (RC-160) or with (6-D-tryptophan)luteinizing hormone-releasing hormone ((D-Trp/sup 6/)LH-RH) delayed delivery systems. After 18 weeks of BOP administration, the hamsters were divided into three groups of 10-20 animals each. Group I consisted of untreated controls, group II was injected with RC-160, and group III was injected with (D-Trp/sub 2/)LH-RH. A striking decrease in tumor weight and volume was obtained in animals treated with (D-Trp/sup 6/)LH-RH or with the somatostatin analog RC-160. After 45 days of treatment with either analog, the survival rate was significantly higher in groups II and III (70%), as compared with the control group (35%). The studies, done by light microscopy, high-resolution microscopy, and electron microscopy, showed a decrease in the total number of cancer cells and changes in the epithelium, connective tissue, and cellular organelles in groups II and III treated with the hypothalamic analogs as compared to controls. These results in female hamsters with induced ductal pancreatic tumors confirm and extend the authors findings, obtained in male animals with transplanted tumors, that (D-Trp/sub 6/)LH-RH and somatostatin analogs inhibit the growth of pancreatic cancers.

  10. Molecular cloning of Senegalese sole (Solea senegalensis) follicle-stimulating hormone and luteinizing hormone subunits and expression pattern during spermatogenesis.

    PubMed

    Cerdà, Joan; Chauvigne, François; Agulleiro, Maria J; Marin, Elena; Halm, Silke; Martínez-Rodríguez, Gonzalo; Prat, Francisco

    2008-05-01

    Pituitary gonadotropins (GTHs), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are key regulators of vertebrate reproduction. However, in teleosts with testis of semi-cystic type and asynchronous spermatogenesis, as the flatfish Senegalese sole (Solea senegalensis), the physiological roles of FSH and LH are still not well understood. To gain insight into this mechanism, full-length complementary DNAs (cDNAs) encoding Senegalese sole FSH beta and LH beta subunits, and the common glycoprotein alpha subunit (CG alpha), were cloned and sequenced. The three cDNAs consisted of 550, 582 and 744 nucleotides encoding peptides of 120, 148 and 132 amino acids, respectively. Comparison of the deduced amino acid sequences of sole FSH beta, LH beta and CG alpha with those from other teleosts indicated that cysteine residues and potential N-linked glycosylation sites were fully conserved with respect to other percomorphs and salmonids. However, the primary structure of FSH beta and LH beta in pleuronectiforms appeared to be highly divergent. In situ hybridization of mature male pituitaries showed that fshb, lhb and cga mRNAs were localized in the proximal pars distalis and in the periphery of pars intermedia. Real-time quantitative reverse transcription-polymerase chain reaction indicated that the levels of all three transcripts in the pituitary of males increased during winter and spring, at the time when plasma levels of androgens raised and testicular germ cell development and spermatozoa production were stimulated. These results suggest that FSH and LH may regulate spermatogenesis in Senegalese sole similarly to that described for other teleosts with testis of cystic type and synchronous germ cell development.

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

    PubMed Central

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

    2016-01-01

    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

  12. Neonatal imprinting predetermines the sexually dimorphic, estrogen-dependent expression of galanin in luteinizing hormone-releasing hormone neurons.

    PubMed Central

    Merchenthaler, I; Lennard, D E; López, F J; Negro-Vilar, A

    1993-01-01

    The incidence of colocalization of galanin (GAL) in luteinizing hormone-releasing hormone (LHRH) neurons is 4- to 5-fold higher in female than male rats. This fact and the finding that the degree of colocalization parallels estradiol levels during the estrous cycle suggest that GAL is an estrogen-inducible product in a subset of LHRH neurons. To analyze further this paradigm we evaluated the effects of gonadectomy and steroid replacement therapy in male and female rats. Ovariectomy resulted in a significant decrease in the number of cells colocalizing LHRH and GAL, whereas estradiol replacement to such animals restored the incidence of colocalization to that observed in controls. In males, however, estradiol treatment failed to enhance the incidence of colocalization of GAL and LHRH, indicating, therefore, that the colocalization of these peptides is gender-determined. This possibility--i.e., gender-specific determination of LHRH neurons coexpressing GAL--was evaluated by neonatal manipulation of hypothalamic steroid imprinting. As mentioned above, male rats did not respond to estrogen or testosterone by increasing GAL/LHRH colocalization as females did. Neonatally orchidectomized rats, whose hypothalami have not been exposed to testosterone during the critical period, when treated with estrogen in adulthood showed an increase in colocalization of GAL and LHRH similar to that seen in female animals. These observations indicate that the colocalization of LHRH/GAL is neonatally determined by an epigenetic mechanism that involves the testis. In summary, this sex difference in the incidence of colocalization of GAL and LHRH represents a unique aspect of sexual differentiation in that only certain phenotypic characteristics of a certain cellular lineage are dimorphic. The subpopulation of LHRH neurons that also produces GAL represents a portion of the LHRH neuronal system that is sexually differentiated and programed to integrate, under steroidal control, a network of

  13. Disrupting the circadian photo-period alters the release of follicle-stimulating hormone, luteinizing hormone, progesterone, and estradiol in maternal and fetal sheep

    PubMed Central

    GAO, Qinqin; LV, Juanxiu; LI, Weisheng; ZHANG, Pengjie; TAO, Jianying; XU, Zhice

    2016-01-01

    Although a large number of studies show that photo-period disruption potentially affects hormone secretion in mammals, information about the effects of circadian photo-period disruption during pregnancy on fetal blood reproductive hormone levels is scarce. This study used ewes and their fetuses to determine the effects of circadian photo-period disruption (deprivation of darkness) on follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone in maternal and fetal circulation at late gestation. Pregnant ewes (gestational age: 135 ± 3 days) were randomly placed into control and dark deprivation groups. The control (N = 5) and dark deprivation (N = 5) groups were exposed to a fixed 12 h light/12 h dark cycle and a 24 h constant light cycle, respectively, for 2 days. Dark deprivation up-regulated follicle-stimulating hormone and estradiol levels and down-regulated progesterone levels in both maternal and fetal circulation, and up-regulated luteinizing hormone levels in fetal but not maternal circulation. These results provide new information about how circadian photo-period disruption during pregnancy could alter the release of certain reproductive hormones into fetal blood, which may influence the development of fetal organs in utero, as well as long-term health. PMID:27319751

  14. Immunodetection of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid stimulating hormone (TSH) and prolactin (PRL) in Brachionus calyciflorus (Rotifera: Monogononta).

    PubMed

    Alvarado-Flores, Jesús; Montoya-Garcia, María Del Rosario; Juárez, Javier Ventura; Rico-Martínez, Roberto

    2009-12-01

    The endocrine system controls and coordinates behavioral, biochemical, and physiological processes through signal mechanisms using neuropeptides or products of neurosecretory cells. Among invertebrates, this system is poorly studied in rotifers, in which estrogens and androgens significantly affect sexual reproduction. This is the first report of the presence of the Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), Thyroid Stimulating Hormone (TSH) and Prolactin (PRL) in rotifers. Analyses included the avidin-biotin-peroxidase complex method with primary antibodies LH (Anti-Rat LH serum for RIA), PRL (Anti-Rat PRL serum for RIA), FSH (Anti-Rat FSH serum for RIA) and TSH (Anti-Rat TSH serum for RIA). These hormones were found in females, males and parthenogenetic and sexual eggs of the freshwater Brachionus calyciflorus. The immunoreactivity of FSH, LH, TSH and PRL in females was observed in: ovaries, cerebrum, mastax, stomach, lorica, and the stomach gland. However, in males LH was observed only at the trochal disk and cerebrum. The hormones FSH, TSH and PRL, were observed in testicles, contractil vesicles, and cementary gland of males. Regarding amictic or parthenogenetic eggs, the hormones LH, FSH, TSH, and PRL were located mainly in the micromeres, and the staining in the macromeres was weak. On the other hand, in the mictic or sexual eggs the inner shell is stained for the hormones PRL and LH, opposite to the staining of FSH and TSH, located mainly in the embryo. In general, immuno-reactivity was observed in areas important for the reproductive, excretory, digestive and developmental processes.

  15. Correlation between the serum luteinizing hormone to folliclestimulating hormone ratio and the anti-Müllerian hormone levels in normo-ovulatory women.

    PubMed

    Lee, Jong Eun; Yoon, Sang Ho; Kim, Hye Ok; Min, Eung Gi

    2015-03-01

    Serum anti-Müllerian hormone (AMH) levels are regarded as an age-specific marker for predicting the ovarian reserve in women of reproductive age. Some studies have shown that the luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio can be used as a predictor of ovarian reserve. The purpose of this study was to assess the variation of LH/FSH ratio with aging and to evaluate the correlation between serum LH/FSH ratio and AMH levels as a predictor of the ovarian reserve in normo-ovulatory women. We retrospectively analyzed the day 3 serum hormone levels in 1,251 patients (age range: 20-50 yr) between January 2010 and January 2011. We divided the patients into 6 groups according to their age. Relation between serum AMH level and LH/FSH ratio was analyzed statistically. The serum AMH level was inversely correlated with age (r = -0.400, P < 0.001). A significant negative correlation was found between serum LH/FSH ratio and age (r = -0.213, P < 0.001). There was a significant partial correlation between serum LH/FSH ratio and AMH level when adjusted by age (r = 0.348, P < 0.001). The LH/FSH ratio could be considered as a useful marker for the ovarian reserve and could be applied to the clinical evaluation with AMH.

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

    SciTech Connect

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

    1987-10-01

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

  17. [Effects of obesity on peak level of luteinizing hormone in gonadotropin-releasing hormone agonist test and obesity-related hormones in girls with central precocious puberty].

    PubMed

    Zhou, Xue-Lian; Fu, Jun-Fen; Jin, Ju-Hua; Dong, Guan-Ping; Jiang, You-Jun; Huang, Ke; Chen, Xue-Feng; Wu, Wei

    2015-08-01

    To explore the effects of obesity on the peak level of luteinizing hormone (LH) in the gonadotropin-releasing hormone (GnRH) agonist test and obesity-related hormones in girls with central precocious puberty (CPP). Three hundred and thirty-three girls with CPP who underwent the GnRH agonist test between 2012 and 2014 were classified into three groups: normal weight (n=123), overweight (n=108), and obesity (n=102), according to body mass index (BMI). The sexual development indices were compared between the three groups. Twenty girls were randomly selected from each group for evaluation of the serum levels of leptin, sex hormone binding globulin (SHBG), neurokinin B, and kisspeptin. The correlation of BMI with the levels of various hormones was assessed using Pearson correlation analysis. There was no significant difference in mean age at diagnosis between the three groups; however, the bone age was significantly higher in the overweight and obesity groups than in the normal weight group (P<0.05). The peak level of LH in the GnRH agonist test and SHBG level in the normal weight group were significantly higher than those in the overweight and the obesity groups, while the serum levels of leptin and neurokinin B were significantly lower in the normal weight group than in the overweight and the obesity groups (P<0.05). BMI was negatively correlated with the peak level of LH in the GnRH agonist test and SHBG level (P<0.05), and positively correlated with the levels of leptin and neurokinin B (P<0.05). The effects of BMI on the result of the GnRH agonist test and levels of obesity-related hormones should be taken into account in girls with precocious puberty.

  18. Kisspeptin receptor agonist (FTM080) increased plasma concentrations of luteinizing hormone in anestrous ewes.

    PubMed

    Whitlock, Brian K; Daniel, Joseph A; Amelse, Lisa L; Tanco, Valeria M; Chameroy, Kelly A; Schrick, F Neal

    2015-01-01

    Kisspeptin receptor (KISS1R) agonists with increased half-life and similar efficacy to kisspeptin in vitro may provide beneficial applications in breeding management of many species. However, many of these agonists have not been tested in vivo. These studies were designed to test and compare the effects of a KISS1R agonist (FTM080) and kisspeptin on luteinizing hormone (LH) in vivo. In experiment 1 (pilot study), sheep were treated with FTM080 (500 pmol/kg BW) or sterile water (VEH) intravenosuly. Blood was collected every 15 min before (1 h) and after (1 h) treatment. In experiment 2, sheep were treated with KP-10 (human Metastin 45-54; 500 pmol/kg BW), one of three dosages of FTM080 (500 (FTM080:500), 2500 (FTM080:2500), or 5000 (FTM080:5000) pmol/kg BW), or VEH intravenously. Blood was collected every 15 min before (1 h) and after (4 h) treatment. In experiment 1, FTM080:500 increased (P < 0.05) plasma LH concentrations when compared to VEH. The area under the curve (AUC) of LH following FTM080:500 treatment was also increased (P < 0.05). In experiment 2, plasma LH concentrations increased (P < 0.05) following treatment with KP-10 and FTM080:5000 when compared to VEH and FTM080:500. The AUC of LH following KP-10 was greater than (P < 0.05) all other treatments and the AUC of LH following FTM080:5000 was greater than (P < 0.05) all treatments except KP-10. These data provide evidence to suggest that FTM080 stimulates the gonadotropic axis of ruminants in vivo. Any increased half-life and comparable efficacy of FTM080 to KP-10 in vitro does not appear to translate to in vivo in sheep.

  19. Performance characteristics of two immunoassays for the measurement of urinary luteinizing hormone.

    PubMed

    Robinson, Neil; Saudan, Christophe; Sottas, Pierre-Edouard; Mangin, Patrice; Saugy, Martial

    2007-01-04

    Urine luteinizing hormone (LH) concentration is routinely measured in all anti-doping laboratories to exclude recombinant LH abuse and to test any potential alteration of the hypophyseal-gonadal axis. Before establishing proper reference values among professional top level athletes, an extended validation of two commercial immunoassays for LH measurements was performed. Elecsys 1010 and Access are two automated immunoanalyzers for central laboratories. The limit of detection, the limit of quantification, intra-laboratory, inter-technique correlation, precision, accuracy were determined. Furthermore, reference urinary LH distribution values for male and female top level athletes were determined. Stability studies of LH in urine following freezing and thawing cycles (n=3) as well as storage conditions at room temperature, 4 degrees C and -20 degrees C were performed. Male and female subjects showed important urinary corrected (specific gravity correction) LH distribution differences. Intra-assay precision for the Access analyzer was less than 8.0% whereas inter-assay was close to 11%. Intra and inter-assay precision for the Elecsys 1010 analyzer was slightly better. A good inter-technique correlation was obtained ([Elecsys 1010]=1.0434[Access]+1.146, R=0.953). No urinary LH loss was observed after two freezing and thawing cycles. On the other hand, time and bad storage conditions such as elevated temperature can deteriorate rapidly urinary LH. In conclusion, both analyzers showed acceptable performances and are suitable for screening anti-doping analyses. Each anti-doping laboratory has to settle its own reference distribution values and then determine when to launch a confirmation procedure. This takes place then depending on the positivity criteria the anti-doping laboratory has established and validated. This study also clearly showed that the time delay between the urine collection and the analysis should be reduced as much as possible and urine samples should be

  20. Kisspeptin receptor agonist (FTM080) increased plasma concentrations of luteinizing hormone in anestrous ewes

    PubMed Central

    Daniel, Joseph A.; Amelse, Lisa L.; Tanco, Valeria M.; Chameroy, Kelly A.; Schrick, F. Neal

    2015-01-01

    Kisspeptin receptor (KISS1R) agonists with increased half-life and similar efficacy to kisspeptin in vitro may provide beneficial applications in breeding management of many species. However, many of these agonists have not been tested in vivo. These studies were designed to test and compare the effects of a KISS1R agonist (FTM080) and kisspeptin on luteinizing hormone (LH) in vivo. In experiment 1 (pilot study), sheep were treated with FTM080 (500 pmol/kg BW) or sterile water (VEH) intravenosuly. Blood was collected every 15 min before (1 h) and after (1 h) treatment. In experiment 2, sheep were treated with KP-10 (human Metastin 45-54; 500 pmol/kg BW), one of three dosages of FTM080 (500 (FTM080:500), 2500 (FTM080:2500), or 5000 (FTM080:5000) pmol/kg BW), or VEH intravenously. Blood was collected every 15 min before (1 h) and after (4 h) treatment. In experiment 1, FTM080:500 increased (P < 0.05) plasma LH concentrations when compared to VEH. The area under the curve (AUC) of LH following FTM080:500 treatment was also increased (P < 0.05). In experiment 2, plasma LH concentrations increased (P < 0.05) following treatment with KP-10 and FTM080:5000 when compared to VEH and FTM080:500. The AUC of LH following KP-10 was greater than (P < 0.05) all other treatments and the AUC of LH following FTM080:5000 was greater than (P < 0.05) all treatments except KP-10. These data provide evidence to suggest that FTM080 stimulates the gonadotropic axis of ruminants in vivo. Any increased half-life and comparable efficacy of FTM080 to KP-10 in vitro does not appear to translate to in vivo in sheep. PMID:26587345

  1. Melatonin effects on luteinizing hormone in postmenopausal women: a pilot clinical trial NCT00288262

    PubMed Central

    Kripke, Daniel F; Kline, Lawrence E; Shadan, Farhad F; Dawson, Arthur; Poceta, J Steven; Elliott, Jeffrey A

    2006-01-01

    Background In many mammals, the duration of the nocturnal melatonin elevation regulates seasonal changes in reproductive hormones such as luteinizing hormone (LH). Melatonin's effects on human reproductive endocrinology are uncertain. It is thought that the same hypothalamic pulse generator may both trigger the pulsatile release of GnRH and LH and also cause hot flashes. Thus, if melatonin suppressed this pulse generator in postmenopausal women, it might moderate hot flashes. This clinical trial tested the hypothesis that melatonin could suppress LH and relieve hot flashes. Methods Twenty postmenopausal women troubled by hot flashes underwent one week of baseline observation followed by 4 weeks of a randomized controlled trial of melatonin or matched placebo. The three randomized treatments were melatonin 0.5 mg 2.5–3 hours before bedtime, melatonin 0.5 mg upon morning awakening, or placebo capsules. Twelve of the women were admitted to the GCRC at baseline and at the end of randomized treatment for 24-hour sampling of blood for LH. Morning urine samples were collected twice weekly to measure LH excretion. Subjective responses measured throughout baseline and treatment included sleep and hot flash logs, the CESD and QIDS depression self-ratings, and the SAFTEE physical symptom inventory. Results Urinary LH tended to increase from baseline to the end of treatment. Contrasts among the 3 randomized groups were statistically marginal, but there was relative suppression combining the groups given melatonin as contrasted to the placebo group (p < 0.01 one-tailed, Mann-Whitney U = 14.) Similar but not significant results were seen in blood LH. There were no significant contrasts among groups in hot flashes, sleep, depression, or side-effect measures and no significant adverse effects of any sort. Conclusion The data are consistent with the hypothesis that melatonin suppresses LH in postmenopausal women. An effect related to the duration of nocturnal melatonin elevation

  2. Is aromatization of testosterone to estradiol required for inhibition of luteinizing hormone secretion in men?

    PubMed Central

    Santen, R J

    1975-01-01

    A variety of studies in man and animals demonstrate that testosterone (T) is aromatized to estradiol (E) in the hypothalamus and limbic system. These observations suggested the possibility that conversion to E is an absolute requirement for the biologic activity of T on the hypothalamic-pituitary axis. Since this hypothesis implies a common mechanism of action of these two steroids, the demonstration of divergent effects of T and E on luteinizing hormone (LH) secretion would exclude this possibility. To test this hypothesis, the actions of T and E on three separate aspects of LH release (mean LH, pulsatile LH secretion, and responsiveness to LH-releasing hormone [LH-RH]) were contrasted. T and E, infused at two times their respective production rates into normal men, reduced mean LH levels similarly during 6 h of steroid infusion and for 6 h thereafter. However, these steroids exerted different effects on pulsatile secretion. E reduced the amplitude of spontaneous LH pulse from pre- and postinfusion control levels of 75+/-14 and 68+/-5.6% (SEM) to 39+/-5.7%. In contrast, T increased pulse amplited to 96+/-14% and decreased pulse frequency from basal levels of 3.4+/-0.31 to 1.8+/-0.31 pulses/6h. The site of suppressive action was determined by administering 25 microgms of LH-RH to the same men during T and E infusions and during three additional control periods without steroid administration. LH-RH produced similar 170-190% increments in serum LH during the three control periods and during T infusion. In contrast, E markedly blunted (76+/-31%, p less than 0.005) the LH response to LH-RH. Under the conditions of acute steroid infusion at doses (utilized in these experiments) producing similar inhibition of mean LH, E but not T acted directly on the pituitary to diminish LH-RH responsiveness. As further support that androgens can act without conversion to estrogens, the effects of a nonaromatizable androgen, dihydrotestosterone (DHT), on mean LH levels were studied

  3. Basic fibroblast growth factor priming increases the responsiveness of immortalized hypothalamic luteinizing hormone releasing hormone neurones to neurotrophic factors.

    PubMed

    Gallo, F; Morale, M C; Tirolo, C; Testa, N; Farinella, Z; Avola, R; Beaudet, A; Marchetti, B

    2000-10-01

    The participation of growth factors (GFs) in the regulation of luteinizing hormone releasing hormone (LHRH) neuronal function has recently been proposed, but little is known about the role played by GFs during early LHRH neurone differentiation. In the present study, we have used combined biochemical and morphological approaches to study the ability of a number of GFs normally expressed during brain development, including basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I) to induce survival, differentiation, proliferation, and phenotypic expression of immortalized (GT1-1) LHRH neurones in vitro, at early (3-days in vitro, 3-DIV) and late (8-DIV) stages of neuronal differentiation. Comparison of GF-treated vs untreated neurones grown in serum-deprived (SD) medium demonstrated bFGF to be the most potent, and insulin the least active in promoting neuronal differentiation. Thus, at both 3-DIV and 8-DIV, but especially at 8-DIV, bFGF induced the greatest increase in the total length and number of LHRH processes/cell and in growth cone surface area. bFGF was also the most active at 3-DIV, and IGF-I at 8-DIV, in counteracting SD-induced cell death, whereas EGF was the most potent in increasing [3H]thymidine incorporation. All GFs studied decreased the spontaneous release of LHRH from GT1-1 cells when applied at 3-DIV or 8-DIV, except for insulin which was inactive at both time-points and bFGF which was inactive at 8-DIV. Pre-treatment of GT1-1 cells with a suboptimal ('priming') dose of bFGF for 12 h followed by application of the different GFs induced a sharp potentiation of the neurotrophic and proliferative effects of the latter and particularly of those of IGF-I. Moreover, bFGF priming counteracted EGF-induced decrease in LHRH release and significantly stimulated LHRH secretion following IGF-I or insulin application, suggesting that bFGF may sensitize LHRH neurones to differentiating effects of

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

    PubMed

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

    2009-07-15

    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 (P<0.01). Location, ovulatory response to first pLH 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 (P<0.01) in the GnRH/PGF/pLH 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

  5. Influences of castration and testosterone on spring to summer changes in release of luteinizing-hormone-releasing hormone in rabbits.

    PubMed

    Lin, W W; Ramirez, V D

    1992-09-01

    Push-pull cannulae were implanted toward the tuberal region of the hypothalamus in ten intact New Zealand male rabbits. In the first experiment, rabbits were perfused at different times after castration: 5-10 days (n = 10), 22-31 days (n = 9) and 50-64 days (n = 8). The release, mean amplitude and mean frequency of luteinizing-hormone-releasing hormone (LHRH) signals from 37 perfusions in ten animals were analysed in intact rabbits and at different times after castration. No significant changes in release of LHRH and in amplitude were observed, but the frequency was significantly higher 22-31 days after castration than in intact rabbits (intact: 0.86 +/- 0.12; castrated: 1.20 +/- 0.13 pulses h-1, P < 0.035; n = 9). In Expt 2, testosterone and placebo Silastic capsules were implanted in the castrated rabbits. Perfusions were performed in the following four periods, defined by season and time after testosterone and placebo implants: (i) spring; before implants, (ii) late spring; 0-2 weeks after implants, (iii) summer solstice; 2-4 weeks after implants and (iv) summer; 4-6 weeks after implants. Castrated rabbits were perfused during spring; castrated rabbits with testosterone capsule implants were perfused during late spring, around summer solstice and in summer and castrated rabbits with placebo implants were perfused during periods (iii) and (iv). Castrated animals with placebo implants showed no significant changes in mean LHRH release and amplitude, although the frequency was significantly higher around the summer solstice period than in castrated rabbits perfused in the spring. In castrated rabbits with testosterone implants LHRH release was significantly higher in late spring than around the summer solstice and in the summer. In addition, the concentrations of LHRH in late spring were significantly higher than those of intact and castrated animals. In contrast, mean LHRH amplitude and frequency did not change. Mean amount of LHRH released and amplitude in

  6. Supression of the steroid-primed luteinizing hormone surge in the female rat by sodium dimethyldithiocarbamate: Relationship to hypothalamic catecholamines and GnRH neuronal activation

    EPA Science Inventory

    In female rodents, hypothalamic norepinephrine (NE) has a role in stimulating the secretion of gonadotropin-releasing hormone (GnRH) that triggers the ovulatory surge of luteinizing hormone (LH). NE synthesis from dopamine requires the presence of dopamine--hydroxylase (DH) an...

  7. Evaluation of the influence of prenatal transportation stress on GnRH-stimulated luteinizing hormone and testosterone secretion in sexually mature Brahman bulls

    USDA-ARS?s Scientific Manuscript database

    This study examined the relationships of prenatal transportation stress (PNS) with cortisol, luteinizing hormone (LH), and testosterone secretion before and after gonadotrophin releashing hormone (GnRH) stimulation of sexually mature Brahman bulls derived from the calf crop of 96 Brahman cows (48 co...

  8. Supression of the steroid-primed luteinizing hormone surge in the female rat by sodium dimethyldithiocarbamate: Relationship to hypothalamic catecholamines and GnRH neuronal activation

    EPA Science Inventory

    In female rodents, hypothalamic norepinephrine (NE) has a role in stimulating the secretion of gonadotropin-releasing hormone (GnRH) that triggers the ovulatory surge of luteinizing hormone (LH). NE synthesis from dopamine requires the presence of dopamine--hydroxylase (DH) an...

  9. Y chromosome haplogroup D2a1 is significantly associated with high levels of luteinizing hormone in Japanese men.

    PubMed

    Sato, Y; Shinka, T; Nozawa, S; Yoshiike, M; Koh, E; Kanaya, J; Namiki, M; Matsumiya, K; Tsujimura, A; Komatsu, K; Itoh, N; Eguchi, J; Yamauchi, A; Iwamoto, T; Nakahori, Y

    2015-05-01

    The association between the Y chromosome haplogroup D2 and risk of azoospermia and low sperm motility has been previously studied, and it was indicated that haplogroups DE (YAP lineage) are associated with prostate cancer risk in Japanese males. Our assumption had been that Y chromosome haplogroups may be associated with sex hormone levels, because sex hormones have been deemed responsible for spermatogenesis and carcinogenesis. In this study, we assessed the association between Y chromosome haplogroups and sex hormone levels, including those of testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin-B, and calculated free testosterone (cFT), in 901 young men from the general Japanese population (cohort 1) and 786 Japanese men of proven fertility (cohort 2). We found that the haplogroup D2a1 was significantly associated with high LH levels in a combined analysis involving two cohorts (β = 0.068, SE = 0.025, p = 0.0075), following correction for multiple testing. To date, this result is the first evidence that implicates Y chromosome haplogroups in an association with sex hormone levels. © 2015 American Society of Andrology and European Academy of Andrology.

  10. Effect of subluteal concentrations of progesterone on luteinizing hormone and ovulation in lactating dairy cows.

    PubMed

    Hatler, T B; Hayes, S H; Ray, D L; Reames, P S; Silvia, W J

    2008-09-01

    Two experiments were conducted to determine if administration of progesterone within a low, subluteal range (0.1-1.0 ng/mL) blocks the luteinizing hormone (LH) surge (experiments 1 and 2) and ovulation (experiment 2) in lactating dairy cows. In experiment 1, progesterone was administered to cycling, lactating dairy cows during the luteal phase of the estrous cycle using a controlled internal drug release (CIDR) device. CIDRs were pre-incubated in other cows for either 0 (CIDR-0), 14 (CIDR-14) or 28 days (CIDR-28). One group of cows received no CIDRs and served as controls. One day after CIDR insertion, luteolysis was induced by two injections of prostaglandin (PG) F(2alpha) (25 mg) at 12 h intervals. Two days after the first injection, estradiol cypionate (ECP; 3 mg) was injected to induce a LH surge. Concentrations of progesterone after luteolysis were 0.11, 0.45, 0.78 and 1.20 ng/mL for cows treated with no CIDR, CIDR-28, CIDR-14, and CIDR-0, respectively. LH surges were detected in 4/4 controls, 4/5 CIDR-28, 2/5 CIDR-14 and 0/5 CIDR-0 cows following ECP. In experiment 2, progesterone was administered to cycling, lactating, Holstein cows during the luteal phase of the estrous cycle as in experiment 1. Luteolysis was induced as in experiment 1. The occurrence of an endogenous LH surge and ovulation were monitored for 7 days. Concentrations of progesterone after luteolysis were 0.13, 0.30, 0.70 and 1.20 ng/mL for cows treated with no CIDR, CIDR-28, CIDR-14 and CIDR-0, respectively. LH surges and ovulation were detected in 5/5 controls, 3/7 CIDR-28, 0/5 CIDR-14 and 0/5 CIDR-0 cows. It was concluded that low concentrations of progesterone can reduce the ability of either endogenous or exogenous estradiol to induce a preovulatory surge of LH and ovulation.

  11. Mechanisms of luteinizing-hormone exocytosis in Staphylococcus aureus-alpha-toxin-permeabilized sheep gonadotropes.

    PubMed Central

    van der Merwe, P A; Millar, R P; Wakefield, I K; Davidson, J S

    1989-01-01

    We have used primary gonadotropes permeabilized with the pore-forming protein Staphylococcus aureus alpha-toxin to investigate luteinizing hormone (lutropin, LH) exocytosis. The diameter of the alpha-toxin pores (2-3 nm) allows the exchange of small molecules, whereas larger cytosolic proteins are retained. Because of the slow exchange of small molecules through the pores, we have developed a protocol which combines prolonged pre-equilibration of the permeabilized cells at 0 degrees C before stimulation with strong Ca2+ buffering. Under these conditions, increasing the free Ca2+ concentration from 0.1 microM to 10 microM [EC50 (concentration effecting half-maximal response) 2-3 microM] resulted in a 15-20-fold increase in LH exocytosis. LH exocytosis was maximal in the first 3 min and completed by 12 min. When permeabilized cells were equilibrated for prolonged periods in the absence of MgATP, Ca2(+)-stimulated LH secretion gradually declined (greater than 90% decrease by 60 min). Addition of MgATP (5 mM) rapidly restored full Ca2(+)-stimulated LH secretion. MgATP supported Ca2(+)-stimulated LH secretion at a half-maximal concentration of 1.5 mM. UTP and adenosine 5'-[gamma-thio]triphosphate were 40 and 31% as effective as MgATP, whereas other nucleotide triphosphates were ineffective. The protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA; 50 nM) stimulated LH exocytosis at free Ca2+ concentrations as low as 1 nM and was additive with Ca2+ at higher free Ca2+ concentrations. PMA-stimulated exocytosis required MgATP at concentrations similar to those required for Ca2(+)-stimulated LH exocytosis. These results demonstrate that LH exocytosis can be triggered both by micromolar Ca2+ concentrations or, in the virtual absence of Ca2+, by PKC activation. Both mechanisms of stimulated exocytosis have an absolute requirement for millimolar ATP. Because they retain cytosolic proteins, alpha-toxin-permeabilized cells may have advantages over alternative

  12. Mechanisms of luteinizing-hormone exocytosis in Staphylococcus aureus-alpha-toxin-permeabilized sheep gonadotropes.

    PubMed

    van der Merwe, P A; Millar, R P; Wakefield, I K; Davidson, J S

    1989-12-15

    We have used primary gonadotropes permeabilized with the pore-forming protein Staphylococcus aureus alpha-toxin to investigate luteinizing hormone (lutropin, LH) exocytosis. The diameter of the alpha-toxin pores (2-3 nm) allows the exchange of small molecules, whereas larger cytosolic proteins are retained. Because of the slow exchange of small molecules through the pores, we have developed a protocol which combines prolonged pre-equilibration of the permeabilized cells at 0 degrees C before stimulation with strong Ca2+ buffering. Under these conditions, increasing the free Ca2+ concentration from 0.1 microM to 10 microM [EC50 (concentration effecting half-maximal response) 2-3 microM] resulted in a 15-20-fold increase in LH exocytosis. LH exocytosis was maximal in the first 3 min and completed by 12 min. When permeabilized cells were equilibrated for prolonged periods in the absence of MgATP, Ca2(+)-stimulated LH secretion gradually declined (greater than 90% decrease by 60 min). Addition of MgATP (5 mM) rapidly restored full Ca2(+)-stimulated LH secretion. MgATP supported Ca2(+)-stimulated LH secretion at a half-maximal concentration of 1.5 mM. UTP and adenosine 5'-[gamma-thio]triphosphate were 40 and 31% as effective as MgATP, whereas other nucleotide triphosphates were ineffective. The protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA; 50 nM) stimulated LH exocytosis at free Ca2+ concentrations as low as 1 nM and was additive with Ca2+ at higher free Ca2+ concentrations. PMA-stimulated exocytosis required MgATP at concentrations similar to those required for Ca2(+)-stimulated LH exocytosis. These results demonstrate that LH exocytosis can be triggered both by micromolar Ca2+ concentrations or, in the virtual absence of Ca2+, by PKC activation. Both mechanisms of stimulated exocytosis have an absolute requirement for millimolar ATP. Because they retain cytosolic proteins, alpha-toxin-permeabilized cells may have advantages over alternative

  13. Somatostatin analogs as adjuncts to agonists of luteinizing hormone-releasing hormone in the treatment of experimental prostate cancer.

    PubMed Central

    Schally, A V; Redding, T W

    1987-01-01

    The combination of a long-acting delivery system for the agonist [D-Trp6]luteinizing hormone-releasing hormone ([D-Trp6]LH-RH) with modern somatostatin analogs was studied in the Dunning R-3327H rat prostate cancer model. Microcapsules of [D-Trp6]LH-RH releasing 25 micrograms/day were injected once a month. In the first experiment the adjunct was the somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), administered at a dose of 2.5 micrograms twice a day, and the therapy was continued for 70 days. Tumor volume was significantly decreased by [D-Trp6]LH-RH microcapsules or RC-121 given alone. The combination of microcapsules and analog RC-121 caused a greater inhibition of tumor growth than the single agents. Similar effects were seen when the percent increase in the tumor volume was examined. The inhibition of tumor growth caused by the [D-Trp6]LH-RH microcapsules was greater than that caused by RC-121. The combination of the two agents was again the most effective, resulting in the smallest increase in tumor volume. Tumor weights were much lower in the groups treated with microcapsules or RC-121 alone than in controls. The lowest tumor weights were obtained in the group that received the combination of [D-Trp6]LH-RH microcapsules and RC-121. Similar results were obtained in the second experiment, in which the animals were treated for a period of 83 days with microcapsules containing the somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) that released 5 micrograms/day and were injected twice a month alone or in combination with microcapsules of [D-Trp6]LH-RH. Microcapsules of analog RC-160 given alone significantly decreased tumor growth as measured by the final tumor volume, the percentage change from the initial tumor volume, and the reduction in tumor weight. The inhibition of tumor growth induced by [D-Trp6]LH-RH microcapsules was greater than that caused by RC-160. The most striking decrease in tumor weight and volume was

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

    PubMed

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

    2017-04-01

    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.

  15. Leucine-enkephalin-like immunoreactivity is localized in luteinizing hormone-producing cells in the axolotl (Ambystoma mexicanum) pituitary.

    PubMed

    Suzuki, Hirohumi; Yamamoto, Toshiharu

    2014-02-01

    In this study, we used immunohistochemical techniques to determine the cell type of leucine-enkephalin (Leu-ENK)-immunoreactive cells in the axolotl (Ambystoma mexicanum) pituitary. Immunoreactive cells were scattered throughout the pars distalis except for the dorso-caudal portion. These cells were immuno-positive for luteinizing hormone (LH), but they were immuno-negative for adrenocorticotrophic, growth, and thyroid-stimulating hormones, as well as prolactin. Immunoelectron microscopy demonstrated that Leu-ENK-like substance and LH co-localized within the same secretory granules. Leu-ENK secreted from gonadotrophs may participate in LH secretion in an autocrine fashion, and/or may participate in the release of sex steroids together with LH. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Gene expression of luteinizing hormone receptor and steroidogenic enzymes during Leydig cell development.

    PubMed

    Abney, T O; Zhai, J

    1998-02-01

    Testicular Leydig cells (LC) are rapidly and selectively destroyed by an injection of ethane dimethane sulfonate (EDS). LC regeneration occurs in the testis of the EDS-treated rats from the differentiation of the precursor Leydig cells (PLC). This study was designed to investigate the patterns of change in the mRNAs for the luteinizing hormone receptor (LHR) and the steroidogenic enzymes, cholesterol side chain cleavage (P-450scc) and 17 alpha-hydroxylase (P-450(17 alpha)) during LC regeneration from PLCs. Mature (60 days of age) Sprague-Dawley male rats received a single intraperitoneal injection of EDS and were killed at different times between days 2 and 60 post-treatment. PLC- and LC-enriched fractions were isolated from the testes of the EDS-treated rats and age-matched control rats using a collagenase digestion-Percoll gradient method. Total RNA was extracted from these cell populations and subjected to Northern blot analysis. The LC fraction isolated from testes of control rats expressed four major transcripts of the LHR, sized 1.8, 2.5, 4.2 and 7.0 kb. The undifferentiated PLC fraction from controls expressed only a truncated form, the 1.8 kb transcript. This truncated LHR transcript was also the only LHR mRNA species detected in PLCs at day 2 post-EDS treatment. In contrast, all four transcripts of the LHR were detected in the PLC fraction at day 10 post-EDS treatment. The levels of the full length 7.0 kb transcript increased thereafter and reached a peak between days 24 and 36 post-EDS treatment in the PLC fraction. Concomitant with the increase in the 7.0 kb transcript, the truncated 1.8 kb transcript decreased in amount and reached a nadir between days 16 and 36 post-treatment. The changes observed in this cell fraction reflect the process of differentiation of PLCs into LCs. At day 45 post-EDS treatment, the level of the 7.0 kb transcript decreased while the 1.8 kb form increased in the PLC fraction, reflecting the completion of LC regeneration from

  17. First attempt to monitor luteinizing hormone and reproductive steroids in urine samples of the Amazonian manatee (Trichechus inunguis).

    PubMed

    Amaral, Rodrigo S; Rosas, Fernando C W; Graham, Laura H; da Silva, Vera M F; Oliveira, Claudio A

    2014-12-01

    The aims of this study were to validate an enzyme immunoassay (EIA) for the measurement of luteinizing hormone (LH) in urine samples of Amazonian manatees (Trichechus inunguis; Mammalia: Sirenia) and to monitor urinary LH and reproductive steroids during the ovarian cycle in this species. Urine samples were collected from two captive males following a hormonal challenge with a gonadotropin-releasing hormone (GnRH) analogue. The urinary LH results from hormonal challenge were compared with urinary androgens for the purpose of EIA validation. Furthermore, urine samples were collected daily, over a 12-wk period, from two captive adult females, for 2 consecutive yr. The urinary LH pattern from females was compared with the patterns of urinary progestagens and estrogen conjugates throughout the ovarian cycle. An LH peak was observed in both male Amazonian manatees after the hormonal challenge, occurring prior to or together with peak androgen levels. In the females, the ovarian cycle ranged from 40 to 48 days (mean of 43.7 days). Two distinct peaks of estrogen conjugates were observed across all cycles analyzed, and the urinary LH peaks observed were accompanied by peaks of urinary estrogen conjugates. The EIA was validated as a method for the quantification of urinary LH from Amazonian manatees, as it was able to detect variations in the levels of LH in urine samples. These results suggest that T. inunguis exhibits a peculiar hormonal pattern during the ovarian cycle. Therefore, further studies are desirable and necessary to clarify the relationship between this hormonal pattern and morphological changes, as well as mating behavior, in Amazonian manatee.

  18. The chromosomal localization of the human follicle-stimulating hormone receptor gene (FSHR) on 2p21-p16 ls similar to that of the luteinizing hormone receptor gene

    SciTech Connect

    Rousseau-Merck, M.F.; Berger, R.; Atger, M.; Loosfelt, H.; Milgrom, E. )

    1993-01-01

    Two cDNA probes (5[prime]and 3[prime]region) corresponding to the human follicle-stimulating hormone receptor gene (FSHR) were used for chromosomal localization by in situ hybridization. The localization obtained on chromosome 2p21-p16 is similar to that of the luteinizing hormone/choriogonadotropin (LH/CG) receptor gene. 24 refs. 1 fig., 1 tab.

  19. Long-acting delivery systems for peptides: inhibition of rat prostate tumors by controlled release of [D-Trp6]luteinizing hormone-releasing hormone from injectable microcapsules.

    PubMed Central

    Redding, T W; Schally, A V; Tice, T R; Meyers, W E

    1984-01-01

    Intramuscular injection of [6-D-tryptophan]-luteinizing hormone-releasing hormone [( D-Trp6]LH-RH) in microcapsules of poly(DL-lactide-co-glycolide), designed to release a controlled dose of the peptide over a 30-day period, decreased the weights of androgen-dependent Dunning prostate tumors in rats and suppressed serum testosterone levels more effectively than daily subcutaneous administration of equivalent or double doses of unencapsulated [D-Trp6]LH-RH. The microcapsules or daily injections of [D-Trp6]LH-RH also significantly decreased tumor volumes. Microcapsules of [D-Trp6]LH-RH or related analogs that can be injected once a month should make the treatment of patients with prostate carcinoma and other neoplasms or disorders more convenient and efficacious. Images PMID:6237365

  20. QSAR models for predicting the activity of non-peptide luteinizing hormone-releasing hormone (LHRH) antagonists derived from erythromycin A using quantum chemical properties.

    PubMed

    Fernández, Michael; Caballero, Julio

    2007-04-01

    Multiple linear regression (MLR) combined with genetic algorithm (GA) and Bayesian-regularized Genetic Neural Networks (BRGNNs) were used to model the binding affinity (pK(I)) of 38 11,12-cyclic carbamate derivatives of 6-O-methylerythromycin A for the Human Luteinizing Hormone-Releasing Hormone (LHRH) receptor using quantum chemical descriptors. A multiparametric MLR equation with good statistical quality was obtained that describes the features relevant for antagonistic activity when the substituent at the position 3 of the erythronolide core was varied. In addition, four-descriptor linear and nonlinear models were established for the whole dataset. Such models showed high statistical quality. However, the BRGNN model was better than the linear model according to the external validation process. In general, our linear and nonlinear models reveal that the binding affinity of the compounds studied for the LHRH receptor is modulated by electron-related terms.

  1. Characterization of recombinant DNA derived-human luteinizing hormone in vitro and in vivo: efficacy in ovulation induction and corpus luteum support

    SciTech Connect

    Simon, J.A.; Danforth, D.R.; Hutchison, J.S.; Hodgen, G.D.

    1988-06-10

    The present data are the first, to the authors knowledge, to demonstrate the production feasibility of a commercially available medication of pure human luteinizing hormone from recombinant DNA technology (rechLH). The rechLH preparation achieved ovulation induction and corpus luteum support in the primate menstrual cycle. The observations described herein indicate the opportunity for significant improvement in the treatment of infertile women and men who require gonadal stimulation. Recombinant DNA-derived gonadotropin products, rechLH in this case, will have several therapeutic advantages compared with current medications extracted from urine. These advantages include (1) better reliability of an available supply of hormone and (2) improved treatment flexibility in determining the optimal dose ratio of follicle-stimulating hormone and luteinizing hormone or avoidance of the long-acting effects of human chorionic gonadotropin, as the needs of individual patients may dictate.

  2. Inhibition of mammary tumor growth in rats and mice by administration of agonistic and antagonistic analogs of luteinizing hormone-releasing hormone.

    PubMed Central

    Redding, T W; Schally, A V

    1983-01-01

    Experiments were undertaken with estrogen-dependent mammary carcinomas in rats and mice to determine the antitumor activities of agonistic and antagonistic analogs of luteinizing hormone-releasing hormone (LH-RH). Chronic administration of the agonist [D-Trp6]LH-RH or of antagonist 1 ( [NAc-D-p-Cl-Phe1,2-Phe3,D-Arg6-D-Ala10]LH-RH) at doses of 25 and 50 micrograms/day, respectively, for 21 days to mice bearing the MXT mammary carcinoma significantly decreased tumor weight and volume. The weight of the ovaries and serum progesterone levels in mice treated with [D-Trp6]LH-RH or antagonist 1 were also significantly reduced. In rats bearing the MT/W9A mammary adenocarcinoma, chronic administration of [D-Trp6]LH-RH at a dose of 25 micrograms twice a day or of antagonist 2 ( [NAc-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH) at a dose of 50 micrograms twice a day for 28 days significantly decreased tumor weight and volume. Chronic treatment with either [D-Trp6]LH-RH or antagonist 2 markedly diminished the weight of the ovaries and serum levels of both estrogen and progesterone. Serum luteinizing hormone was significantly decreased in rats treated with antagonist 2 but not in rats treated with [D-Trp6]LH-RH. There was a significant drop in serum prolactin levels in rats treated with [D-Trp6]LH-RH but not in those receiving antagonist 2. Regression of mammary tumors in rats and mice in response to chronic administration of [D-Trp6]LH-RH and the two antagonistic analogs of LH-RH suggests that these compounds should be considered for the development of a new hormone therapy for breast cancer in women. PMID:6219395

  3. Luteinizing hormone (LH)-releasing hormone agonist reduces serum adrenal androgen levels in prostate cancer patients: implications for the effect of LH on the adrenal glands.

    PubMed

    Nishii, Masahiro; Nomura, Masashi; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Ito, Kazuto; Oyama, Tetsunari; Suzuki, Kazuhiro

    2012-01-01

    Recently, adrenal androgens have been targeted as key hormones for the development of castration-resistant prostate cancer therapeutics. Although circulating adrenal androgens originate mainly from the adrenal glands, the testes also supply about 10%. Although widely used in androgen deprivation medical castration therapy, the effect of luteinizing hormone-releasing hormone (LH-RH) agonist on adrenal androgens has not been fully studied. In this study, changes in testicular and adrenal androgen levels were measured and compared to adrenocorticotropic hormone levels. To assess the possible role of LH in the adrenal glands, immunohistochemical studies of the LH receptor in normal adrenal glands were performed. Forty-seven patients with localized or locally progressive prostate cancer were treated with LH-RH agonist with radiotherapy. Six months after initiation of treatment, testosterone, dihydrotestosterone, and estradiol levels were decreased by 90%-95%, and dehydroepiandrosterone-sulfate, dehydroepiandrosterone, and androstenedione levels were significantly decreased by 26%-40%. The suppressive effect of LH-RH agonist at 12 months was maintained. Adrenocorticotropic hormone levels showed an increasing trend at 6 months and a significant increase at 12 months. LH receptors were positively stained in the cortex cells of the reticular layer of the adrenal glands. The long-term LH-RH agonist treatment reduced adrenal-originated adrenal androgens. LH receptors in the adrenal cortex cells of the reticular layer might account for the underlying mechanism of reduced adrenal androgens.

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

    PubMed

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

    2013-06-01

    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 (<7.0 mm) was unaffected, although subsequent growth of a dominant follicle (>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

  5. [Role of estrogen-sensitive neurons in the arcuate region of the hypothalamus in the mechanism of luteinizing hormone release].

    PubMed

    Babichev, V N; Ignatkov, V Ia

    1978-01-01

    Experiments were conducted on rats; estradiol brought to the arcuate region of the hypothalamus by means of microionophoresis led to the increase of the region of the hypothalamus by means of microionophoresis led to the increase of the blood luteinizing hormone (LH) level during the following stages of the estral cycle-diestrus 1, diestrus 2, and the first half day of the proestrus; as to the second half of the proestrus day--estradiol decreased its level. Changes in the LH level in the hypophysis under the influence of the microionophoretic introduction of estradiol into the arcuate region occurred during the second half of the day of diestrus 2 (reduction), and during the estrus (elevation). In the majority of cases a rise of the blood level was combined with the neuron activation in the arcuate region under the influence of estradiol.

  6. Ablation of GalNAc-4-sulfotransferase-1 enhances reproduction by altering the carbohydrate structures of luteinizing hormone in mice

    PubMed Central

    Mi, Yiling; Fiete, Dorothy; Baenziger, Jacques U.

    2008-01-01

    Luteinizing hormone (LH), produced in the anterior lobe of the pituitary, is a member of the hypothalamic-pituitary-gonad axis that is required for production of the sex hormones estradiol, progesterone, and testosterone. Perturbations in levels of hormones associated with this axis can result in defects in sexual development and maturity. LH bears unique N-linked carbohydrate units that terminate with a sulfated N-acetylgalactosamine structure (GalNAc-4-SO4) that mediates its clearance from the blood. To determine the significance of this terminal structure, we ablated the gene encoding the sulfotransferase responsible for sulfate addition to GalNAc on LH, GalNAc-4-sulfotransferase-1 (GalNAc-4-ST1) in mice. Mice lacking GalNAc-4-ST1 exhibited increased levels of circulating LH. In male mice, this resulted in elevated levels of testosterone and precocious maturation of testis and seminal vesicles. Female mice lacking GalNAc-4-ST1 demonstrated elevated estrogen levels and exhibited precocious sexual maturation and increased fecundity. Female mice remained in estrus for prolonged periods and produced almost 50% more litters per mouse than wild-type mice over the same period of time. Thus, sulfate modification of the terminal glycosylation of LH plays a central role in regulating the hypothalamic-pituitary-gonad axis in vivo. PMID:18431515

  7. Urinary profiles of luteinizing hormone, estrogen and progestagen during the estrous and gestational periods in giant pandas (Ailuropda melanoleuca)

    PubMed Central

    Cai, Kailai; Yie, Shangmian; Zhang, Zhihe; Wang, Juan; Cai, Zhigang; Luo, Li; Liu, Yuliang; Wang, Hairui; Huang, He; Wang, Chengdong; Huang, Xiangming; Lan, Jingchao; Hou, Rong

    2017-01-01

    Luteinizing hormone (LH) is one of the main pituitary hormones that regulate ovulation, however its role has not been studied in giant panda. In this study, we developed an ELISA method for the detection of panda urinary LH. We analyzed urinary hormones of 24 female pandas during 36 breeding periods, we found females could easily be impregnated if the first mating occurred within 10 hours after LH peak. We also found the patterns of the ratios of urinary LH and progestagen in pandas that bred and successfully gave birth were significantly different from those that bred but failed to give birth. These data was the first to provide the urinary LH profiles during the estrous and gestational periods in pandas, and demonstrated that the appearance of the urinary LH peak indicated the timing of ovulation. The LH detection together with estrogen analysis makes the window for successful mating narrower than previously reported. Moreover, detection of urinary LH and progestagen can be used to discriminate between pregnancies and pseudopregnancies/miscarriages in the species. Thus, our findings suggest that LH not only plays a critical role in regulating ovulation but also plays an important role in maintaining pregnancy in the giant panda. PMID:28091600

  8. Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis

    SciTech Connect

    Hsueh, A.J.W.; Dahl, K.D.; Vaughan, J.; Tucker, E.; Rivier, J.; Bardin, C.W.; Vale, W.

    1987-07-01

    Inhibin, a gonadal hormone capable of preferential suppression of pituitary follicle-stimulating hormone (FSH) secretion, has recently been purified. The major form of this protein is an ..cap alpha beta.. heterodimer encoded by two separate genes. In contrast to the FSH-suppressing action of the ..cap alpha beta.. heterodimer, the ..beta beta.. homodimer stimulates FSH secretion. Luteinizing hormone (LH)-secreting pituitary cells and gonadal androgen-producing cells have long been shown to form a closed-loop feedback axis. Based on recent studies demonstrated the FSH stimulation of inhibin biosynthesis by ovarian granulosa and testis Sertoli cells, an additional closed-loop feedback axis exists between pituitary FSH- and gonadal inhibin-producing cells. Because uncharacterized Sertoli cell factors have been suggested to either stimulate or inhibit androgen production by testicular Leydig cells, the authors have tested the intragonadal paracrine actions of heterodimers and homodimers of inhibin subunits. In primary cultures of testis cells, the ..cap alpha beta.. heterodimer of inhibin enhances Leydig cell androgen biosynthesis stimulated by LH, whereas the ..beta beta.. homodimer suppresses androgen production. The data indicate that the inhibin-related gene products synthesized by Sertoli and granulosa cells may form heterodimers or homodimers to serve as intragonadal paracrine signals in the modulation of LH-stimulated androgen biosynthesis and allow cross-communication between the two feedback loops.

  9. Urinary profiles of luteinizing hormone, estrogen and progestagen during the estrous and gestational periods in giant pandas (Ailuropda melanoleuca).

    PubMed

    Cai, Kailai; Yie, Shangmian; Zhang, Zhihe; Wang, Juan; Cai, Zhigang; Luo, Li; Liu, Yuliang; Wang, Hairui; Huang, He; Wang, Chengdong; Huang, Xiangming; Lan, Jingchao; Hou, Rong

    2017-01-16

    Luteinizing hormone (LH) is one of the main pituitary hormones that regulate ovulation, however its role has not been studied in giant panda. In this study, we developed an ELISA method for the detection of panda urinary LH. We analyzed urinary hormones of 24 female pandas during 36 breeding periods, we found females could easily be impregnated if the first mating occurred within 10 hours after LH peak. We also found the patterns of the ratios of urinary LH and progestagen in pandas that bred and successfully gave birth were significantly different from those that bred but failed to give birth. These data was the first to provide the urinary LH profiles during the estrous and gestational periods in pandas, and demonstrated that the appearance of the urinary LH peak indicated the timing of ovulation. The LH detection together with estrogen analysis makes the window for successful mating narrower than previously reported. Moreover, detection of urinary LH and progestagen can be used to discriminate between pregnancies and pseudopregnancies/miscarriages in the species. Thus, our findings suggest that LH not only plays a critical role in regulating ovulation but also plays an important role in maintaining pregnancy in the giant panda.

  10. Radioimmunoassay for 6-D-tryptophan analog of luteinizing hormone-releasing hormone: measurement of serum levels after administration of long-acting microcapsule formulations.

    PubMed Central

    Mason-Garcia, M; Vigh, S; Comaru-Schally, A M; Redding, T W; Somogyvari-Vigh, A; Horvath, J; Schally, A V

    1985-01-01

    A sensitive and specific radioimmunoassay for [6-D-tryptophan]luteinizing hormone-releasing hormone [( D-Trp6]LH-RH) was developed and used for following the rate of liberation of [D-Trp6]LH-RH from a long-acting delivery system based on a microcapsule formulation. Rabbit antibodies were generated against [D-Trp6]LH-RH conjugated to bovine serum albumin with glutaraldehyde. Crossreactivity with LH-RH was less than 1%; there was no significant crossreactivity with other peptides. The minimal detectable dose of [D-Trp6]LH-RH was 2 pg per tube. Intra- and interassay coefficients of variation were 8% and 10%, respectively. The radioimmunoassay was suitable for direct determination of [D-Trp6]LH-RH in serum, permitting the study of blood levels of the analog after single injections into normal men and after once-a-month administration of microcapsules to rats. In men, 90 min after subcutaneous injection of 250 micrograms of the peptide, serum [D-Trp6]LH-RH rose to 6-12 ng/ml. Luteinizing hormone was increased 90 min and 24 hr after the administration of the analog. Several batches of microcapsules were tested in rats and the rate of release of [D-Trp6]LH-RH was followed. The improved batch of microcapsules of [D-Trp6]LH-RH increased serum concentrations of the analog for 30 days or longer after intramuscular injection. This was accompanied by suppression of testosterone levels for more than 30 days. This radioimmunoassay should be of value for monitoring [D-Trp6]LH-RH during long-term therapy. PMID:3156381

  11. Impact of infertility regimens on breast cancer cells: follicle-stimulating hormone and luteinizing hormone lack a direct effect on breast cell proliferation in vitro.

    PubMed

    Boukaidi, Samir Alexandre; Cooley, Anne; Hardy, Ashley; Matthews, Laura; Zelivianski, Stanislav; Jeruss, Jacqueline S

    2012-02-01

    To examine the impact of hormones used for controlled ovarian hyperstimulation (COH) on normal and malignant breast cell growth and proliferation. In vitro study of cultured normal and malignant breast cell lines. Academic medical center. None. Normal and malignant breast cell lines cultured in two- and three-dimensional (2D and 3D) systems and treated with follicle-stimulating hormone (FSH), luteinizing hormone (LH), or FSH with LH or human chorionic gonadotropin (hCG). Effects of treatment on cell proliferation in 2D culture using the MTS assay and on colony growth in 3D culture. Compared with untreated cells, normal MCF-10A cells showed a decrease in proliferation and colony size when exposed to a combination of FSH and hCG. The HCC 1937 cells treated with FSH and LH also showed a decrease in colony growth but no change in proliferation. None of the treatments had an effect on the proliferation or colony size of the MCF-7 cells. Follicle-stimulating hormone, LH, and hCG do not appear to cause an increase in cell proliferation or colony growth in either normal or malignant mammary epithelial cell lines. The potential risk for mammary cell transformation associated with these agents may be related to indirect endocrine effects on breast cell physiology. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Luteinizing hormone downregulation but not estrogen replacement improves ovariectomy-associated cognition and spine density loss independently of treatment onset timing

    PubMed Central

    Blair, Jeffrey A.; Palm, Russell; Chang, Jaewon; McGee, Henry; Zhu, Xiongwei; Wang, Xinglong; Smith, Gemma Casadesus

    2015-01-01

    Age-related changes in reproductive hormone levels are a well-known risk factor for the development of cognitive dysfunction and dementia in women. We and others have shown an important contribution of gonadotropins in this process. Lowering serum gonadotropin levels is able to rescue cognitive function in Alzheimer’s disease and menopause models, but whether this is time-dependent and the exact mechanism through which gonadotropins regulate cognitive function is unknown. We show that pharmacologically lowering serum levels of luteinizing hormone lead to cognitive improvement immediately after ovariectomy and with a 4 month interval after ovariectomy, when the benefits of 17β-estradiol are known to disappear in rodents. Importantly, we show that these improvements are associated with spine density changes at both time points. These findings suggest a role of luteinizing hormone in learning and memory and neuroplasticity processes as well as provide an alternative therapeutic strategy of menopause associated cognitive loss. PMID:26497249

  13. The effect of porcine luteinizing hormone in the synchronization of ovulation and corpus luteum development in nonlactating cows.

    PubMed

    Ree, T O; Colazo, M G; Lamont, A G A; Kastelic, J P; Dyck, M K; Mapletoft, R J; Ametaj, B N; Ambrose, D J

    2009-07-01

    The objective of this study was to determine the effects of different doses of porcine luteinizing hormone (pLH) versus 100 microg gonadotropin-releasing hormone (GnRH) on ovulatory response (during diestrus and proestrus) and corpus luteum (CL) development in nonlactating cows. In Experiment 1, 75 cows received an intravaginal insert containing 1.9 g progesterone (P4) for 10 d to synchronize estrus (Day 0), with prostaglandin F(2 alpha) (PGF) at insert removal. On Day 5, all follicles >or=8mm were ablated, and on Day 12, cows received 8, 12.5, or 25mg pLH or 100 microg GnRH. Mean (+/-SEM) plasma P4 concentrations on Day 12 did not differ among treatments (5.6+/-0.2 ng/mL). Mean plasma LH concentration was greatest (P<0.01) in cows given 25mg pLH (4.3+/-0.4 ng/mL). The ovulatory response to 25mg pLH (84%) or 100 microg GnRH (72%) was greater (P<0.05) than that to 8 mg pLH (32%), but not different from that of 12.5mg pLH (58%). In Experiment 2, 68 cows were given two injections of PGF 10d apart to synchronize estrus (Day 0). On Day 7, cows received PGF, and, 36 h later, pLH or GnRH (as in Experiment 1). The interval from treatment to ovulation was most variable in cows given 8 mg pLH; only 65% of these cows ovulated during the initial 27 h versus 88% of cows given 25mg pLH (P<0.05). Cows given 25mg pLH or 100 microg GnRH had larger CL area and greater plasma P4 concentrations (P<0.05) than that of those given 8 mg pLH. In summary, diestrous cows given 25mg pLH had the greatest plasma luteinizing hormone concentrations, but ovulatory response did not differ from that of those given 100 microg GnRH. Proestrous cows given 25mg pLH or 100 microg GnRH had greater CL area and P4 concentrations than that of those given 8 mg pLH.

  14. Negative energy balance in a male songbird, the Abert's towhee, constrains the testicular endocrine response to luteinizing hormone stimulation

    PubMed Central

    Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L.; Deviche, Pierre

    2015-01-01

    ABSTRACT 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. PMID:26333925

  15. Prolactin independent rescue of mouse corpus luteum life span: identification of prolactin and luteinizing hormone target genes

    PubMed Central

    Bachelot, Anne; Beaufaron, Julie; Servel, Nathalie; Kedzia, Cécile; Monget, Philippe; Kelly, Paul A.; Gibori, Geula; Binart, Nadine

    2009-01-01

    The corpus luteum (CL) plays a central role in the maintenance of pregnancy in rodents, mainly by secreting progesterone. Female mice lacking prolactin (PRL) receptor (R) are sterile due to a failure of embryo implantation, which is a consequence of decreased luteinizing hormone (LH) receptor expression in the CL and inadequate levels of progesterone. We attempted to treat PRLR−/− females with human chorionic gonadotropin (hCG) and showed a de novo expression of LHR mRNA in the corpora lutea. Binding analysis confirmed that the LHR in hCG-treated PRLR−/− animals was functional. This was accompanied with increased expression of steroidogenic enzymes involved in progesterone synthesis. Despite these effects, no embryo implantation was observed because of high expression of 20α-hydroxysteroid dehydrogenase. To better appreciate the molecular mechanisms underlying maintenance of the CL, a series of mRNA expression-profiling experiments was performed on isolated corpora lutea of PRLR−/− and hCG-treated PRLR−/− mice. This approach revealed several novel candidate genes with potentially pivotal roles in ovarian function, among them, p27, VE-cadherin, Pten, and sFRP-4, a member of the Wnt/frizzled family. This study showed the differential role of PRL and LH in CL function and identified new targets of these hormones in luteal cells. PMID:19531635

  16. Commercial radioimmunoassay for beta subunit of human chorionic gonadotropin: falsely positive determinations due to elevated serum luteinizing hormone

    SciTech Connect

    Fowler, J.E. Jr.; Platoff, G.E.; Kubrock, C.A.; Stuzman, R.E.

    1982-01-01

    Among 17 men who had received seemingly curative treatment for unilateral non-seminomatous germ cell tumors for the testis and who had consistently normal serum human chorionic gonadotropin (HCG) levels at a reference laboratory, 7 (41%) had at least one falsely positive commercial serum HCG determination. To investigate the cause of these falsely positive determinations the authors measured the cross reactivity of luteinizing hormone (LH) and follicle stimulating hormone (FSH) standards in the commercial HCG assay, and studied the relationships between commercial HCG levels and serum LH levels, serum FSH levels and gonadal status in men with and without normal gonadal function. The falsely positive HCG determinations appeared to be due to elevated serum LH levels and cross reactivity of LH in the commercial HCG assay because: 1) there was substantial cross reactivity of the LH standards in the commercial assay, 2) the serum LH was elevated in four of six men with solitary testes, 3) there was a striking correlation between elevated serum LH levels and falsely elevated commercial HCG levels in ten men with solitary or absent testes, and 4) there were no falsely positive HCG determinations in 13 normal men but there were falsely positive HCG determinations in seven of ten anorchid men.

  17. Negative energy balance in a male songbird, the Abert's towhee, constrains the testicular endocrine response to luteinizing hormone stimulation.

    PubMed

    Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L; Deviche, Pierre

    2015-09-01

    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.

  18. Negative energy balance in a male songbird, the Abert's Towhee, constrains the testicular endocrine response to luteinizing hormone stimulation.

    PubMed

    Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L; Deviche, Pierre

    2015-07-10

    Energy deficiency can suppress reproductive functions 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 has 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 (T) 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 T response to GnRH challenge. Energy deficiency did, however, decrease the plasma T responsiveness to LH challenge. Collectively, these observations suggest that energy deficiency has direct gonadal effects consisting in 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.

  19. Food availability affects orexin a/ hypocretin-1-induced inhibition of pulsatile luteinizing hormone secretion in female rats.

    PubMed

    Furuta, Miyako; Mitsushima, Dai; Shinohara, Kazuyuki; Kimura, Fukuko; Funabashi, Toshiya

    2010-01-01

    Orexin A/hypocretin-1 inhibits pulsatile luteinizing hormone (LH) secretion in female rats. In this study, we investigated whether this inhibition was tied to the fasting state, as suggested by our previous study. We first examined whether orexin A inhibited pulsatile LH secretion when food was available ad libitumduring blood sampling. Next, we investigated the effect of intravenous administration of glucose (400 mg/kg) or lactic acid (negative control; 400 mg/kg) on orexin A-induced inhibition of pulsatile LH secretion. We found that orexin A did not affect pulsatile LH secretion in the presence of food, although it increased feeding behavior. Injection of orexin A significantly inhibited pulsatile LH secretion when food was withheld during blood sampling (p < 0.05); this inhibitory effect was rapidly reversed by intravenous injection of glucose but not lactic acid. Because orexin A did not seem to affect pulsatile LH secretion when food was available ad libitum, we speculate that orexin A has an effect on LH secretion when orexin A-induced hunger is accompanied by stress, such as the absence of food. Furthermore, glucose as well as food may act as a satiety factor in gonadotropin-releasing hormone pulse generation. Copyright 2009 S. Karger AG, Basel.

  20. The luteinizing hormone surge is preceded by an estrogen-induced increase of hypothalamic progesterone in ovariectomized and adrenalectomized rats.

    PubMed

    Micevych, Paul; Sinchak, Kevin; Mills, Richard H; Tao, Leslie; LaPolt, Philip; Lu, John K H

    2003-07-01

    As circulating estrogen levels rise on the afternoon of proestrus, they stimulate the hypothalamo-pituitary axis. This estrogen positive feedback is pivotal to stimulate the luteinizing hormone (LH) surge required for ovulation and luteinization of ovarian follicles. In addition to estrogen, pre-LH surge progesterone is critical for an LH surge as was demonstrated by blocking progesterone synthesis. In ovariectomized (OVX) rats treated with trilostane, a blocker of the enzyme 3beta-hydroxysteroid dehydrogenase (3beta-HSD) that catalyzes the conversion of pregnenolone to progesterone, estrogen did not induce an LH surge. Further, estrogen induced an LH surge in OVX and adrenalectomized (ADX) rats, indicating that the source of progesterone was neither the ovary nor adrenal gland. This estrogen-only LH surge was inhibited by pretreatment with trilostane, indicating that although the adrenal gland and ovary were not necessary for positive feedback, progesterone synthesis was critical for estrogen-induced positive feedback in an OVX/ADX rat. This suggested that the LH surge is dependent on the pre-LH surge synthesis of progesterone. Estrogen-induced progesterone receptors in the hypothalamus are vital for the LH surge, so a potential location for progesterone synthesis is the hypothalamus. OVX/ADX female rats were treated with 17beta-estradiol (50 microg) and progesterone levels were assayed by RIA. Progesterone levels were elevated in hypothalamic tissue following estrogen treatment. No increases in tissue progesterone levels were found in parietal cortex, cerebellum, medulla, pituitary or plasma. Additionally, male rats that do not have an estrogen positive feedback-induced LH surge were examined. Castrated/ADX male rats had no increase in hypothalamic progesterone levels after estrogen treatment. Together, these data strongly suggest that estrogen enhances neuroprogesterone synthesis in the hypothalamus that is involved in the positive feedback regulating the LH

  1. Interleukin 1. alpha. inhibits prostaglandin E sub 2 release to suppress pulsatile release of luteinizing hormone but not follicle-stimulating hormone

    SciTech Connect

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

    1991-04-01

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

  2. Aromatase inhibitors with or without luteinizing hormone-releasing hormone agonist for metastatic male breast cancer: report of four cases and review of the literature.

    PubMed

    Kuba, Sayaka; Ishida, Mayumi; Oikawa, Masahiro; Nakamura, Yoshiaki; Yamanouchi, Kosho; Tokunaga, Eriko; Taguchi, Kenichi; Esaki, Taito; Eguchi, Susumu; Ohno, Shinji

    2016-11-01

    The roles of aromatase inhibitors (AIs) and luteinizing hormone-releasing hormone (LH-RH) agonists in the management of male breast cancer remain uncertain, with no reports in Japanese men. We report four Japanese male patients with metastatic breast cancer treated with AIs with or without an LH-RH agonist, and consider the relationship between treatment effect and estradiol (E2) concentration. Three patients were initially treated with AI alone after selective estrogen receptor modulators (SERMs), and one received AIs plus an LH-RH agonist after a SERM. Two patients treated with an AI alone responded, one patient with E2 levels below the lower assay limit and the other with levels above the limit. The other treated with an AI alone experienced progression regardless of the E2 levels below the lower assay limit, however, responded after the addition of an LH-RH agonist. E2 concentrations were related to the efficacy of treatment in one patient. The patient initially treated with an AI plus an LH-RH agonist also responded. No grade 3 or 4 adverse events were observed in any of the patients treated with AIs with or without an LH-RH agonist. AIs with or without an LH-RH agonist offer an effective treatment option for hormone receptor-positive metastatic male breast cancer.

  3. Effect of daily administration of 0.5 mg. of chlormadinone acetate on plasma levels of follicle-stimulating hormone, luteinizing hormone, and progesterone during the menstrual cycle.

    PubMed

    Saunders, D M; Marcus, S L; Saxena, B B; Beling, C G; Connell, E B

    1971-05-01

    Investigators at Cornell University Medical College and New York Medical College in New York City studied the effects of chlormadinone acetate administration on hormone levels in an effort to better understand the contraceptive mode of action of this drug. 9 healthy women had 2 consecutive cycles studied. While the first cycle was a control cycle, the second one involved chlormadinone acetate administration, .5 mg/day from Day 1 to Day 28 or until the occurrence of spontaneous menstruation if this delayed until after Day 28. Basal body temperature was recorded each morning. Chlormadinone tended to suppress the mean luteinizing hormone and follicle stimulating hormone peaks and the plasma progesterone levels. 3 patients are believed to have ovulated during the experimental cycle, but probably in 2 of them the luteal phase was less pronounced than a normal luteal phase. However, 1 of the remaining 6 patients had failed to ovulate in the control cycle. Though limitations exist in the study of the parameters investigated here, such study is necessary since direct evidence of ovulation (e.g., pregnancy, observation of corpus luteum) is usually unobtainable.

  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.

    PubMed

    Fortes, Marina R S; Reverter, Antonio; Hawken, Rachel J; Bolormaa, Sunduimijid; Lehnert, Sigrid A

    2012-09-01

    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. Molecular and biological interaction between major histocompatibility complex class I antigens and luteinizing hormone receptors or beta-adrenergic receptors triggers cellular response in mice.

    PubMed Central

    Solano, A R; Cremaschi, G; Sánchez, M L; Borda, E; Sterin-Borda, L; Podestá, E J

    1988-01-01

    Purified IgG from BALB/c mouse anti-C3H serum exerts positive inotropic and chronotropic effects in C3H mouse atria and induces testosterone synthesis in C3H mouse Leydig cells. The effect depends on IgG concentration and can be abolished by beta-adrenergic-receptor and luteinizing hormone-receptor antagonists. IgG interferes with the binding of dihydroalprenolol and luteinizing hormone. Monoclonal antibodies against major histocompatibility complex class I antigens were active on the Leydig cells of C3H and BALB/c mice. There was a parallelism between the effect of each individual monoclonal antibody with specificity for a particular haplotype and the response of the target cell from the strains carrying such haplotypes. These antibodies could precipitate the soluble luteinizing hormone-receptor complex. The results suggested that bound hormone triggers the association of major histocompatibility class I antigen with the receptor, thereby activating the respective target cells. PMID:2839829

  6. Effects of luteinizing hormone-releasing hormone and arginine-vasotocin on the sperm-release response of Günther's Toadlet, Pseudophryne guentheri

    PubMed Central

    2010-01-01

    Background Luteinizing hormone-releasing hormone (LHRH) is an exogenous hormone commonly used to induce spermiation in anuran amphibians. Over the past few decades, the LHRH dose administered to individuals and the frequency of injection has been highly variable. The sperm-release responses reported have been correspondingly diverse, highlighting a need to quantify dose-response relationships on a species-specific basis. This study on the Australian anuran Pseudophryne guentheri first evaluated the spermiation response of males administered one of five LHRHa doses, and second, determined whether AVT administered in combination with the optimal LHRHa dose improved sperm-release. Methods Male toadlets were administered a single dose of 0, 1, 2, 4 or 8 micrograms/g body weight of LHRHa. A 4 micrograms/g dose of AVT was administered alone or in combination with 2 micrograms/g LHRHa. Spermiation responses were evaluated at 3, 7 and 12 h post hormone administration (PA), and sperm number and viability were quantified using fluorescent microscopy. Results LHRHa administration was highly effective at inducing spermiation in P. guentheri, with 100% of hormone-treated males producing sperm during the experimental period. The number of sperm released in response to 2 micrograms/g LHRHa was greater than all other doses administered and sperm viability was highest in the 1 microgram/g treatment. The administration of AVT alone or in combination with LHRHa resulted in the release of significantly lower sperm numbers. Conclusion Overall, results from this study suggest that in P. guentheri, LHRHa is effective at inducing spermiation, but that AVT inhibits sperm-release. PMID:21059269

  7. Luteinizing hormone, sex steroids and extracorporeal circulation - a promising link to treat retroperitoneal sarcomas. A reconsideration of cancer treatment.

    PubMed

    Lazar, Angela Madalina

    2012-10-01

    Retroperitoneal sarcomas are rare and aggressive tumors with a negative prognosis as there is currently no satisfactory treatment for them. The only proven factor that can significantly increase the otherwise poor survival of sarcoma patients is the radically of resection. However, the completeness of resection is hindered by the hypervascularized nature of sarcomas and the frequent involvement of major blood vessels. In this context, we propose to operate on retroperitoneal sarcomas only with the use of extracorporeal circulation, applying vascular clamps above and below the tumor, even with short periods of hypothermic circulatory arrest in complex cases. This technique would allow the surgeon to achieve complete tumor resections, approach large blood vessels easier and perform sofisticated vascular reconstructions with no fear of hemorrhage which is fundamental to achieve a bloodless surgical field. Also, we speculate on the etiology of retroperitoneal sarcomas that appear mostly during the period of menopause/andropause. Although both estrogens and androgens have been incriminated in inducing various cancer types, including sarcomas, an endogenous estradiol cathabolyte has been shown to have anti-tumor effects. Considering that during menopause/andropause sex steroid levels actually decrease, our second working hypothesis is that the increasing follicle-stimulating hormone (FSH) and especially luteinizing hormone (LH) levels, together with the relative estrogen/androgen imbalance, may be the triggering cause. Also, a certain level of estrogens (Methoxyestradiol) may be essential in limiting tumor development and dedifferentiation. Given that extragonadal sarcomas appear to behave as endocrine tumors, a targeted hormonal therapy, together with controlled radical resections in complex cases of tumor vascular involvement, would certainly provide a strong link to both prevention and treatment of retroperitoneal sarcomas and even of cancer in general.

  8. Autocrine role of estrogens in the augmentation of luteinizing hormone receptor formation in cultured rat granulosa cells.

    PubMed

    Kessel, B; Liu, Y X; Jia, X C; Hsueh, A J

    1985-06-01

    The effects of estrogens on gonadotropin-stimulated luteinizing hormone (LH) receptor formation were examined in primary cultures of rat granulosa cells. Granulosa cells were cultured for 3 days with increasing concentrations of follicle-stimulating hormone (FSH) in the presence or absence of native and synthetic estrogens. Follicle-stimulating hormone stimulated LH receptor formation in a dose-dependent fashion, and estrogens enhanced the FSH-stimulated LH receptor content by decreasing the apparent ED50 of FSH. At 6.25 ng/ml FSH, the enhancement in LH receptor was estrogen dose dependent, with an ED50 value of about 3 X 10(-9) M for 17 beta-estradiol. The increased LH receptor content seen in cells treated with FSH and estrogen was correlated with increased cAMP production by these cells in response to LH stimulation. Time course studies revealed enhancement of FSH-stimulated LH receptor induction at 48 and 72 h of culture. Granulosa cells were also cultured with FSH for 2 days to induce functional LH receptors, then further cultured for 3 days with LH in the presence or absence of estrogens. At 30 ng/ml LH, increasing concentrations of estrogens maintained LH receptor content in a dose-dependent fashion, with their relative estrogenic potencies in keeping with reported binding affinities to estrogen receptors. An autocrine role of estrogens on LH receptor formation was further tested in granulosa cells treated with FSH and an aromatase substrate (androstenedione) to increase estrogen biosynthesis. Cotreatment with semipurified estrogen antibodies partially blocked the FSH stimulation of LH receptors, whereas nonimmune serum was ineffective. Also, inclusion of diethylstilbestrol prevented the inhibitory effect of the estrogen antibodies. Thus, local estrogens in ovarian follicles may play an autocrine role in granulosa cells to enhance LH receptor formation and to increase granulosa cell responsiveness to the LH surge, with subsequent ovulation and adequate

  9. Association of a missense mutation in the luteinizing hormone/choriogonadotropin receptor gene (LHCGR) with superovulation traits in Chinese Holstein heifers

    PubMed Central

    2012-01-01

    Background Upon binding luteinizing hormone in the ovary, the luteinizing hormone/choriogonadotropin receptor (LHCGR) is necessary for follicular maturation and ovulation, as well as luteal function. We detected mutations in the LHCGR gene and evaluated their association with superovulation. Methods Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing, we examined polymorphisms in LHCGR and the genotypes associated with superovulation traits in 127 Chinese Holstein heifers. Results A G/T polymorphism (ss52050737) in exon 11 was significantly associated with the total number of ova and the number of transferable embryos. Conclusions LHCGR may be a new predictor for superovulation in Chinese Holstein heifers. PMID:23140330

  10. Brainstem projections to the medial preoptic region containing the luteinizing hormone-releasing hormone perikarya in the rat. An immunohistochemical and retrograde transport study.

    PubMed

    Castañeyra-Perdomo, A; Pérez-Delgado, M M; Montagnese, C; Coen, C W

    1992-05-11

    The afferent projections to the anterior medial preoptic area (MPA) from the brainstem have been studied, in female Wistar rats, by retrograde tracing with horseradish peroxidase (HRP). The HRP was injected by iontophoresis into the preoptic region containing the luteinizing hormone-releasing hormone (LHRH) perikarya. The brain sections including the MPA were reacted with diaminobenzidine (DAB) to reveal the injection site; the LHRH cells were then immunohistochemically identified using DAB with ammonium nickel sulphate. When the injection site incorporated the LHRH cells, the brainstem sections were reacted with the DAB nickel solution to detect lysosomal HRP and then immunohistochemically processed to locate the adrenaline-synthesizing cells using DAB alone. The results confirm the brainstem projections to the MPA from the central grey matter, ventral tegmental area, subcoeruleus area, the dorsal raphe nucleus, the lateral parabrachial nucleus, the raphe pontis nucleus, the raphe obscurus nucleus, the region of the paragigantocellular nucleus and the nucleus of the solitary tract. Given the considerable evidence implicating the ascending adrenergic systems in the regulation of LHRH, we focused our attention on the afferents from the locus coeruleus, area postrema and the adrenaline-synthesizing cell groups (C1-3). The only cells which were retrogradely labelled and immunopositive for phenylethanolamine N-methyltransferase were found in C3.

  11. Identification of major urinary metabolites of nafarelin acetate, a potent agonist of luteinizing hormone-releasing hormone, in the rhesus monkey

    SciTech Connect

    Chan, R.L.; Chaplin, M.D.

    1985-09-01

    Nafarelin acetate (less than Glu-His-Trp-Ser-Tyr-3-(2-naphthyl)-D-Ala-Leu-Arg-Pro-Gly-NH2) is a potent agonistic analogue of luteinizing hormone-releasing hormone. After a single iv administration of nafarelin acetate (with UC label at C-3 of 3-(2-naphthyl)-D-Ala) to female rhesus monkeys, about 80% of the radioactivity was eliminated in urine. Five major radioactive urinary metabolites were isolated and purified by reversed phase HPLC. Four of these metabolites, identified by amino acid analysis, were short peptides: the 5-10-hexapeptide amide, the 6-10-pentapeptide amide, the 5-7-tripeptide, and the 6-7-dipeptide. The fifth metabolite, which accounted for about 15% of the radioactivity administered, was shown by NMR and mass spectrometry to be 2-naphthylacetic acid. A possible pathway of its formation is by oxidative deamination of 3-(2-napthyl)-D-Ala to give the corresponding alpha-keto acid, followed by oxidative decarboxylation of the alpha-keto acid. These five metabolites together accounted for about 70% of the radioactivity recovered in the urine of rhesus monkeys, or more than half of the radioactivity in the administered dose. Nafarelin acetate was also present in small amounts. Several of these metabolites were also present in plasma of the rhesus monkey.

  12. Inhibition of growth of a prolactin-secreting pituitary tumor in rats by analogs of luteinizing hormone-releasing hormone and somatostatin.

    PubMed Central

    de Quijada, M G; Redding, T W; Coy, D H; Torres-Aleman, I; Schally, A V

    1983-01-01

    We investigated the effects of [D-Trp6]LH-RH [agonistic analog of luteinizing hormone-releasing hormone (LH-RH)], N-Ac-[D-p-Cl-Phe1,2,D-Trp3,D-Phe6,D-Ala10]LH-RH (antagonistic analog), and [D-5-methoxy-Trp8]somatostatin (somatostatin analog) on the growth of the prolactin and corticotropin-secreting pituitary tumor 7315a in female Buffalo rats. Chronic administration of [D-Trp6]LH-RH in a dose of 25 micrograms/day, starting 18 days after inoculation with the tumor, inhibited the growth of the pituitary tumor. Tumor weight and volume also were reduced when this agonist was administered 3 days after inoculation. The antagonistic LH-RH analog, injected in a dose of 50-100 micrograms for 14-24 days, also significantly inhibited the growth of pituitary tumor. Chronic administration of the somatostatin analog in a dose of 25 micrograms twice a day likewise decreased tumor weights in comparison with controls. The inhibition of pituitary tumor growth by LH-RH agonist, LH-RH antagonist, and somatostatin analog was accompanied by a decrease in serum prolactin levels. It was concluded that LH-RH agonist, LH-RH antagonist, and somatostatin analog can inhibit the growth of estrogen-dependent prolactin/corticotropin-secreting pituitary tumor in rats. PMID:6134284

  13. Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

    PubMed Central

    Taheri, Azade; Dinarvand, Rassoul; Atyabi, Fatemeh; Ahadi, Fatemeh; Nouri, Farank Salman; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Borougeni, Atefeh Taheri; Mansoori, Pooria

    2011-01-01

    Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX. PMID:21845098

  14. Seasonal expressions of follicle-stimulating hormone receptor and luteinizing hormone receptor in the scented gland of the male muskrat (Ondatra zibethicus).

    PubMed

    Zhang, Haolin; Zhang, Fengwei; Zhu, Manyu; Wang, Junjie; Sheng, Xia; Yuan, Zhengrong; Han, Yingying; Watanabe, Gen; Taya, Kazuyoshi; Weng, Qiang

    2017-04-01

    Accumulating evidence has shown that follicle-stimulating hormone (FSH) and luteinizing hormone (LH) may influence the functions of nongonadal tissues in addition to their classic target gonads. Our previous studies revealed that the scented glands of male muskrats expressed prolactin receptor, steroidogenic enzymes, and inhibin/activin subunits. To further seek the evidence of the activities of pituitary gonadotropins in scented glands, we investigated the seasonal expression patterns of FSH receptor (FSHR) and LH/choriogonadotropin receptor (LHCGR). The weight and size of scented glands during the breeding season were significantly higher than those during the nonbreeding season. Immunohistochemical studies showed that FSHR was present in the serous cells of scented glands, whereas LHCGR was present in the interstitial cells. The protein and mRNA expression levels of FSHR and LHCGR were significantly higher in the scented glands during the breeding season than those during the nonbreeding season. Importantly, the levels of circulating FSH and LH were remarkably higher during the breeding season. Taken together, these results suggested that gonadotropins may affect the function of muskrat scented gland via the locally expressed receptors in a season-dependent manner.

  15. Luteinizing hormone-releasing hormone targeted poly(methyl vinyl ether maleic acid) nanoparticles for doxorubicin delivery to MCF-7 breast cancer cells.

    PubMed

    Varshosaz, Jaleh; Jahanian-Najafabadi, Ali; Ghazzavi, Jila

    2016-08-01

    The purpose of this study was to design a targeted anti-cancer drug delivery system for breast cancer. Therefore, doxorubicin (DOX) loaded poly(methyl vinyl ether maleic acid) nanoparticles (NPs) were prepared by ionic cross-linking method using Zn(2+) ions. To optimise the effect of DOX/polymer ratio, Zn/polymer ratio, and stirrer rate a full factorial design was used and their effects on particle size, zeta potential, loading efficiency (LE, %), and release efficiency in 72 h (RE72, %) were studied. Targeted NPs were prepared by chemical coating of tiptorelin/polyallylamin conjugate on the surface of NPs by using 1-ethyl-3-(3-dimethylaminopropyl) carboiimid HCl as cross-linking agent. Conjugation efficiency was measured by Bradford assay. Conjugated triptorelin and targeted NPs were studied by Fourier-transform infrared spectroscopy (FTIR). The cytotoxicity of DOX loaded in targeted NPs and non-targeted ones were studied on MCF-7 cells which overexpress luteinizing hormone-releasing hormone (LHRH) receptors and SKOV3 cells as negative LHRH receptors using Thiazolyl blue tetrazolium bromide assay. The best results obtained from NPs prepared by DOX/polymer ratio of 5%, Zn/polymer ratio of 50%, and stirrer rate of 960 rpm. FTIR spectrum confirmed successful conjugation of triptorelin to NPs. The conjugation efficiency was about 70%. The targeted NPs showed significantly less IC50 for MCF-7 cells compared to free DOX and non-targeted NPs.

  16. Physiological role of alpha-melanocyte-stimulating hormone in modulating the secretion of prolactin and luteinizing hormone in the female rat.

    PubMed Central

    Khorram, O; Bedran de Castro, J C; McCann, S M

    1984-01-01

    Long-term ovariectomized (OVX) rats were injected in the third cerebral ventricle with 5 microliter of the globulin fraction of an antiserum raised against alpha-melanocyte-stimulating hormone (alpha-MSH) or an equal volume of the globulin fraction of normal rabbit serum (NRS). Immunoneutralization of brain alpha-MSH produced an increase in the area under the secretion curve of prolactin (Prl), the amplitude of Prl pulses, and mean plasma Prl (P less than 0.01). In animals that had received two injections of NRS or anti-MSH and were subjected to a 2-min ether stress, Prl levels significantly increased within 5 minutes in the NRS-injected rats, whereas Prl levels in the antiserum-injected rats did not increase any further from the initially high baseline levels. The administration of antibodies against alpha-MSH produced a small increase (P less than 0.05) in the area under the secretion of luteinizing hormone (LH) and mean plasma LH; however, the number of LH pulses was unaffected. We conclude that endogenous alpha-MSH of central origin is a physiological neuromodulator of release of Prl and LH in the OVX rat and is involved in the stress-induced release of Prl. PMID:6595673

  17. Direct evidence of estrogen modulation of pituitary sensitivity to luteinizing hormone-releasing factor during the menstrual cycle.

    PubMed Central

    Wang, C F; Yen, S S

    1975-01-01

    To delineate the role of estradiol in the augmented pituitary gonadotropin responsiveness to synthetic luteinizing hormone releasing factor (LRF) seen during high-estrogen phases of the ovulatory cycles (late follicular and midluteal phases), the anti-estrogenic effect of clomiphene citrate (Clomid) on pituitary response to LRF was evaluated during different phases of the ovulatory cycle. Clomid administration (100 mg/day times 5 days) completely negates the augmented gonadotropin responses to LRF (150 mug) during late follicular and midluteal phases observed during the control studies. Thus, a quantitatively and qualitatively similar pituitary sensitivity to LRF during three distinct phases of the menstrual cycle was induced by Clomid treatment that resembles the LRF responsiveness of themale pituitary. The present study demonstrates the pituitary component of the estrogen-induced changes in the sensitivity to LRF. From this and previous data, we conclude that the increases of estradiol secretion associated with the follicular maturation and corpus luteum formation represent a major component of the feedback signal in the modulation of cyclic gonadotropin release occasioned in a large measure by the augmented pituitary sensitivity to LRF. PMID:1088908

  18. Aging and luteinizing hormone effects on reactive oxygen species production and DNA damage in rat Leydig cells.

    PubMed

    Beattie, Matthew C; Chen, Haolin; Fan, Jinjiang; Papadopoulos, Vassilios; Miller, Paul; Zirkin, Barry R

    2013-04-01

    We observed previously that after long-term suppression of luteinizing hormone (LH) and thus of Leydig cell steroidogenesis, restimulation of the Leydig cells by LH resulted in significantly higher testosterone production than by age-matched cells from control rats. These studies suggest that stimulation over time may elicit harmful effects on the steroidogenic machinery, perhaps through alteration of the intracellular oxidant-to-antioxidant balance. Herein we compared the effects of LH stimulation on stress response genes, formation of intracellular reactive oxygen species (ROS), and ROS-induced damage to ROS-susceptible macromolecules (DNA) in young and in aged cells. Microarray analysis indicated that LH stimulation resulted in significant increases in expression of genes associated with stress response and antiapoptotic pathways. Short-term LH treatment of primary Leydig cells isolated from young rats resulted in transiently increased ROS levels compared to controls. Aged Leydig cells also showed increased ROS soon after LH stimulation. However, in contrast to the young cells, ROS production peaked later and the time to recovery was increased. In both young and aged cells, treatment with LH resulted in increased levels of DNA damage but significantly more so in the aged cells. DNA damage levels in response to LH and the levels of intracellular ROS were highly correlated. Taken together, these results indicate that LH stimulation causes increased ROS production by young and aged Leydig cells and that while DNA damage occurs in cells of both ages, there is greater damage in the aged cells.

  19. Genetic ablation of luteinizing hormone receptor improves the amyloid pathology in a mouse model of Alzheimer disease.

    PubMed

    Lin, Jing; Li, Xian; Yuan, Fangping; Lin, Ling; Cook, Christine L; Rao, Ch V; Lei, Zhenmin

    2010-03-01

    Amyloid-beta peptide (Abeta) plays an essential pathophysiologic role in Alzheimer disease, and elevation of luteinizing hormone (LH) levels during aging has been implicated in its pathogenesis. To assess the effect of LH receptor deficiency on Abeta accumulation, we generated a bigenic mouse model, APPsw(+)/Lhr(-/-), which expresses human amyloid precursor protein (APPsw) in the background of LH receptor (Lhr) knockout. Genetic ablation of Lhr resulted in a significant decrease in the number of Abeta plaques and protein content in the hippocampus and cerebral cortex in both male and female mice. Accordingly, several Abeta deposition-related neuropathologic features and functionally relevant molecules were markedly improved, including decreased astrogliosis, reductions of elevated phosphorylated tau, c-fos, alpha7-nicotinic acetylcholine receptor, and restoration of the altered neuropeptide Y receptors Y1 and Y2. Diminution of Abeta accumulation in the absence of LH receptor supports the contention that dysregulation of LH may impact the pathogenesis of Alzheimer disease. The APPsw(+)/Lhr(-/-) mouse may be a useful tool for advancing understanding of the role of LH-mediated events in Alzheimer disease and a model in which to test therapeutic interventions.

  20. Polymorphisms of the bovine luteinizing hormone/choriogonadotropin receptor (LHCGR) gene and its association with superovulation traits.

    PubMed

    Yang, Wu-Cai; Tang, Ke-Qiong; Li, Shu-Jing; Chao, Lu-Ming; Yang, Li-Guo

    2012-03-01

    The major limitation to the development of embryo transfer technique in cattle is the highly variable between individuals in ovulatory response to FSH-induced superovulation. The objective of this study was to identify a predictor to forecast superovulation response on the basis of associations between superovulation performance and gene polymorphism, variation in the bovine luteinizing hormone/choriogonadotropin receptor (LHCGR) gene was investigated using PCR-single-strand conformational (PCR-SSCP) and DNA sequencing. Four single nucleotide polymorphisms (SNPs) of G51656T, A51703G, A51726G and G51737A were identified at the intron 9 of the LHCGR gene in 171 Chinese Holstein cows treated for superovulation, and evaluated its associations with superovulatory response. Association analysis showed that these four SNPs had significant effects on the total number of ova (TNO) (P < 0.05). Moreover, the A51703G and A51726G polymorphisms significantly associated with the number of transferable embryos (NTE) (P < 0.05). In addition, significant additive effect on TNO was detected in polymorphisms of G51656T (P < 0.05) and A51703G (P < 0.01), and the A51703G polymorphism also had significant additive effects on NTE (P < 0.01). These results indicate that LHCGR gene is a potential marker for superovulation response and can be used to predict the most appropriate dose of FSH for superovulation in Chinese Holstein cows.

  1. The Luteinizing Hormone Receptor-Activated Extracellularly Regulated Kinase-1/2 Cascade Stimulates Epiregulin Release from Granulosa Cells

    PubMed Central

    Andric, Nebojsa; Ascoli, Mario

    2008-01-01

    We examine the pathways involved in the luteinizing hormone receptor (LHR)-dependent activation of the epidermal growth factor (EGF) network using cocultures of LHR-positive granulosa cells and LHR-negative test cells expressing an EGF receptor (EGFR)-green fluorescent protein fusion protein. Activation of the LHR in granulosa cells results in the release of EGF-like growth factors that are detected by measuring the phosphorylation of the EGFR-green fluorescent protein expressed only in the LHR-negative test cells. Using neutralizing antibodies and real-time PCR, we identified epiregulin as the main EGF-like growth factor produced upon activation of the LHR expressed in immature rat granulosa cells, and we show that exclusive inhibition or activation of the ERK1/2 cascade in granulosa cells prevents or enhances epiregulin release, respectively, with little or no effect on epiregulin expression. These results show that the LHR-stimulated ERK1/2 pathway stimulates epiregulin release. PMID:18653716

  2. Thyrotropin-luteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyrotropin receptor function

    SciTech Connect

    Nagayama, Yuji; Wadsworth, H.L.; Chazenbalk, G.D.; Russo, D.; Seto, Pui; Rapoport, B. Univ. of California, San Francisco )

    1991-02-01

    To define the sites in the extracellular domain of the human thyrotropin (TSH) receptor that are involved in TSH binding and signal transduction the authors constructed chimeric thyrotropin-luteinizing hormone/chorionic gonadotropin (TSH-LH/CG) receptors. The extracellular domain of the human TSH receptor was divided into five regions that were replaced, either singly or in various combinations, with homologous regions of the rat LH/CG receptor. The chimeric receptors were stably expressed in Chinese hamster ovary cells. The data obtained suggest that the carboxyl region of the extracellular domain (amino acid residues 261-418) and particularly the middle region (residues 171-260) play a role in signal transduction. The possibility is also raised of an interaction between the amino and carboxyl regions of the extracellular domain in the process of signal transduction. In summary, these studies suggest that the middle region and carboxyl half of the extracellular domain of the TSH receptor are involved in signal transduction and that the TSH-binding region is likely to span the entire extracellular domain, with multiple discontinuous contact sites.

  3. Corpus luteum derived copper, zinc-superoxide dismutase serves as a luteinizing hormone-release inhibiting factor in sheep.

    PubMed

    Al-Gubory, Kaïs H; Huet, Jean-Claude; Pernollet, Jean-Claude; Martal, Jacques; Locatelli, Alain

    2003-01-31

    In the present study, we report the purification and characterization of a polypeptide from the sheep corpus luteum of pregnancy with a potent luteinizing hormone-release inhibiting factor (LH-RIF) bioactivity that stained as a single band in SDS-PAGE with an apparent molecular mass of 16000 Da. The amino acid sequences obtained after sequence analysis of peptides derived from the trypsin digestion of LH-RIF were subjected to a protein data bank search and were found to be identical with regions of sheep copper, zinc-superoxide dismutase (Cu,Zn-SOD). The measured mass of LH-RIF (15604.2+/-1.9 Da) was found to be similar to the theoretical mass of sheep Cu,Zn-SOD (15603.5 Da), with a disulfide bond and N acetylated alanine at the N-terminus. The inhibitory action of Cu,Zn-SOD on pulsatile LH secretion would suggest that this antioxidant may play an important role, either independently or in concert with some neurotransmitters, in the neuroendocrine regulation of sheep female reproductive function.

  4. Infertility in Female Mice with a Gain-of-Function Mutation in the Luteinizing Hormone Receptor Is Due to Irregular Estrous Cyclicity, Anovulation, Hormonal Alterations, and Polycystic Ovaries.

    PubMed

    Hai, Lan; McGee, Stacey R; Rabideau, Amanda C; Paquet, Marilène; Narayan, Prema

    2015-07-01

    The luteinizing hormone receptor, LHCGR, is essential for fertility in males and females, and genetic mutations in the receptor have been identified that result in developmental and reproductive defects. We have previously generated and characterized a mouse model (KiLHR(D582G)) for familial male-limited precocious puberty caused by an activating mutation in the receptor. We demonstrated that the phenotype of the KiLHR(D582G) male mice is an accurate phenocopy of male patients with activating LHCGR mutations. In this study, we observed that unlike women with activating LHCGR mutations who are normal, female KiLHR(D582G) mice are infertile. Mice exhibit irregular estrous cyclicity, anovulation, and precocious puberty. A temporal study from 2-24 wk of age indicated elevated levels of progesterone, androstenedione, testosterone, and estradiol and upregulation of several steroidogenic enzyme genes. Ovaries of KiLHR(D582G) mice exhibited significant pathology with the development of large hemorrhagic cysts as early as 3 wk of age, extensive stromal cell hyperplasia and hypertrophy with luteinization, numerous atretic follicles, and granulosa cell tumors. Ovulation could not be rescued by the addition of exogenous gonadotropins. The body weights of the KiLHR(D582G) mice were higher than wild-type counterparts, but there was no increase in the body fat composition or metabolic abnormalities such as impaired glucose tolerance and insulin resistance. These studies demonstrate that activating LHCGR mutations do not produce the same phenotype in female mice as in humans and clearly illustrate species differences in the expression and regulation of LHCGR in the ovary, but not in the testis. © 2015 by the Society for the Study of Reproduction, Inc.

  5. Serum luteinizing hormone level and luteinizing hormone/follicle-stimulating hormone ratio but not serum anti-Müllerian hormone level is related to ovarian volume in Korean women with polycystic ovary syndrome.

    PubMed

    Chun, Sungwook

    2014-06-01

    The aim of the present study was to investigate the relationship between ovarian follicle count and volume on ultrasonography and serum hormone levels including the levels of the anti-Müllerian hormone (AMH) and gonadotropin in women with the polycystic ovary syndrome (PCOS). A total of 118 Korean women aged 18-35 years who were newly diagnosed with PCOS at a university hospital were included in this study. Serum LH, FSH, and AMH levels were measured in the early follicular phase, and the total antral follicle count (TFC) and the total ovarian volume (TOV) were assessed by ultrasonography. The correlations between serum hormonal parameters and ultrasonography characteristics in women with PCOS were evaluated using Pearson's correlation coefficients and a linear regression analysis. Serum AMH levels were significantly correlated with serum LH levels and LH/FSH ratios, and TFC and TOV were significantly correlated with each other on ultrasonography. Serum AMH and LH levels and the LH/FSH ratio were significantly correlated with TFC. Statistically significant correlations between TOV and the LH level (r=0.208, p=0.024) and the LH/FSH ratio (r=0.237, p=0.010) were observed. However, the serum AMH level was not significantly correlated with the ovarian volume, and this result did not change after adjusting for age and body mass index. Serum AMH is not related to the ovarian volume in women with PCOS. My results suggest that serum LH level and the LH/FSH ratio may be more useful than the serum AMH level for representing the status of the ovarian volume in women with PCOS.

  6. Luteinizing hormone stimulation of in vitro ovulation in brook trout (Salvelinus fontinalis) involves follicle contraction and activation of proteolytic genes.

    PubMed

    Crespo, Diego; Pramanick, Kousik; Goetz, Frederick W; Planas, Josep V

    2013-07-01

    Luteinizing hormone (LH) is an essential hormone for the stimulation of the ovulatory process in vertebrates. However, little is known in fish regarding the different mechanisms induced by LH during ovulation that facilitate the rupture of the follicle wall and the subsequent expulsion of the mature oocyte. In this study, the effects of salmon LH (sLH) on in vitro ovulation were investigated in brook trout (Salvelinus fontinalis) isolated follicles. sLH significantly stimulated in vitro ovulation and contraction of brook trout preovulatory follicles. In order to investigate the possible involvement of proteolytic events in the ovulatory action of LH, the expression of genes known to have a crucial role in the degradation of follicle wall structure was examined. Our results show that sLH clearly stimulated the mRNA expression levels of matrix metalloproteinases (MMPs; including mmp2 and mmp19) and other enzymes with proteolytic action during ovulation, such as a disintegrin and metalloproteinase with thrombospondin-like motifs 1 (adamts1) and plasminogen (plg), in brook trout preovulatory follicles. In addition, the expression of mmp2, adamts1 and plg increased in brook trout follicles during the progression of LH-induced ovulation. Interestingly, the expression of tissue inhibitor of matrix metalloproteinase 2 (timp2), a known regulator of MMP2 activity, paralleled that of mmp2, suggesting the existence of a controlled mechanism of MMP2 action. Therefore, the known increase in proteolytic activity during ovulation in fish could be the result of the stimulation of the expression of proteolytic enzymes by LH in preovulatory follicles. We propose that LH may stimulate ovulation in brook trout follicles by stimulating proteolysis of the follicle wall and by stimulating follicle contraction. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Effects of Exposure to Male Goat Hair Extracts on Luteinizing Hormone Secretion and Neuronal Activation in Seasonally Anestrous Ewes

    PubMed Central

    OHARA, Hiromi; MOGI, Kazutaka; ICHIMARU, Toru; OHKURA, Satoshi; TAKEUCHI, Yukari; MORI, Yuji; OKAMURA, Hiroaki

    2014-01-01

    ABSTRACT In sheep and goats, exposure of seasonally anestrous females to males or their fleece/hair activates the gonadotropin-releasing hormone (GnRH) pulse generator leading to pulsatile luteinizing hormone (LH) secretion. Pheromones emitted by sexually mature males are thought to play a prominent role in this male effect. In the present study, we first aimed to clarify whether the male goat pheromone is effective in ewes. Seasonally anestrous St. Croix ewes were exposed to hair extracts derived from either intact or castrated (control) male Shiba goats. The male goat-hair extract significantly increased LH secretion compared to the control, suggesting that an interspecies action of the male pheromone occurs between sheep and goats. Using the male goat-hair extract as the pheromone source, we then aimed to clarify the neural pathway involved in the signal transduction of the male pheromone. Ewes were exposed to either the goat-hair extract or the control and sacrificed 2 hr after the exposure. Expression of c-Fos, a marker of neuronal activation, was immunohistochemically examined. The male goat-hair extract significantly increased the c-Fos expression compared to the control in regions of the vomeronasal system, such as the accessory olfactory bulb and medial amygdala, and the arcuate nucleus. The main olfactory bulb did not exhibit any significant increase in the c-Fos expression by the male goat-hair extract. This result suggests that the neural signal of the male pheromone is conveyed to the GnRH pulse generator through the activated regions in ewes. PMID:24942115

  8. Intraventricular injection of agents that enhance cyclic adenosine monophosphate formation leads to inhibition of proestrous luteinizing hormone surge in rats.

    PubMed

    Taleisnik, S; Haymal, B; Caligaris, L

    1993-09-01

    The effect of increasing hypothalamic levels of 3',5'-cyclic adenosine monophosphate (cAMP) on the preovulatory surge of luteinizing hormone (LH) and ovulation was studied in cycling rats. Animals hearing chronically implanted guiding cannulae into the third ventricle were injected with agents known to enhance the cellular levels of cAMP. Hourly blood samples from the unanesthetized, unrestrained rats were obtained between 11.00 and 17.00 h through a plastic cannula inserted into the jugular vein. Intraventricular injections of serotonin (7.5 mg/ml; 2 microliters) in the morning of proestrous blocked the preovulatory surge of LH and ovulation. This effect was assigned to an increased neuronal level of cAMP because it was prevented by a serum anti-cAMP. Third-ventricle injections of 2 microliters of forskolin (0.5 mmol/l), guanosine 5'-O-(3-thiotriphosphate)(2 mmol/l) or dibutyryl-cAMP (1 mmol/l) at 11.00 h on the day of proestrus mimicked the inhibitory effect of serotonin on the proestrous release of LH. It is suggested that serotonin inhibits LH surge by acting directly on LH-releasing hormone neurons and/or on neurons that provide inputs to these neurons involving cAMP as a second messenger. Neurons releasing gamma-aminobutyric acid (GABA) may serve as interneurons sensitive to serotonin, as well as to cAMP, inasmuch as the inhibitory effect of forskolin on the release of LH was partially blocked by the GABA antagonists, picrotoxin and bicuculline.

  9. Effects of luteinizing hormone and androgen on the development of rat progenitor Leydig cells in vitro and in vivo

    PubMed Central

    Guo, Jing-Jing; Ma, Xue; Wang, Claire QF; Ge, Yu-Fei; Lian, Qing-Quan; Hardy, Dianne O; Zhang, Yu-Fei; Dong, Qiang; Xu, Yun-Fei; Ge, Ren-Shan

    2013-01-01

    Progenitor Leydig cells are derived from stem cells. The proliferation and differentiation of progenitor Leydig cells significantly contributes to Leydig cell number during puberty. However, the regulation of these processes remains unclear. The objective of the present study was to determine whether luteinizing hormone (LH) or androgen contributes to the proliferation and differentiation of progenitor Leydig cells. Fourteen-day-old male Sprague–Dawley rats were treated for 7 days with NalGlu, which is a gonadotropin-releasing hormone antagonist, to reduce the secretion of LH in the pituitary and thus, androgen in the testis. Rats were co-administered with LH or 7α-methyl-nortestosterone (MENT), which is an androgen resistant to metabolism by 5α-reductase 1 in progenitor Leydig cells, and the subsequent effects of LH or androgen were measured. 3H-Thymidine was also intravenously injected into rats to study thymidine incorporation in progenitor Leydig cells. Progenitor Leydig cells were examined. NalGlu administration reduced progenitor Leydig cell proliferation by 83%. In addition, LH or MENT treatment restored Leydig cell proliferative capacity to 73% or 50% of control, respectively. The messenger RNA levels of proliferation-related genes were measured using real-time PCR. The expression levels of Igf1, Lifr, Pdgfra, Bcl2, Ccnd3 and Pcna were upregulated by MENT, and those of Pdgfra, Ccnd3 and Pcna were upregulated by LH. Both LH and MENT stimulated the differentiation of progenitor Leydig cells in vitro. We concluded that both LH and MENT were involved in regulating the development of progenitor Leydig cells. PMID:23792342

  10. Effects of luteinizing hormone and androgen on the development of rat progenitor Leydig cells in vitro and in vivo.

    PubMed

    Guo, Jing-Jing; Ma, Xue; Wang, Claire Q F; Ge, Yu-Fei; Lian, Qing-Quan; Hardy, Dianne O; Zhang, Yu-Fei; Dong, Qiang; Xu, Yun-Fei; Ge, Ren-Shan

    2013-09-01

    Progenitor Leydig cells are derived from stem cells. The proliferation and differentiation of progenitor Leydig cells significantly contributes to Leydig cell number during puberty. However, the regulation of these processes remains unclear. The objective of the present study was to determine whether luteinizing hormone (LH) or androgen contributes to the proliferation and differentiation of progenitor Leydig cells. Fourteen-day-old male Sprague-Dawley rats were treated for 7 days with NalGlu, which is a gonadotropin-releasing hormone antagonist, to reduce the secretion of LH in the pituitary and thus, androgen in the testis. Rats were co-administered with LH or 7α-methyl-nortestosterone (MENT), which is an androgen resistant to metabolism by 5α-reductase 1 in progenitor Leydig cells, and the subsequent effects of LH or androgen were measured. (3)H-Thymidine was also intravenously injected into rats to study thymidine incorporation in progenitor Leydig cells. Progenitor Leydig cells were examined. NalGlu administration reduced progenitor Leydig cell proliferation by 83%. In addition, LH or MENT treatment restored Leydig cell proliferative capacity to 73% or 50% of control, respectively. The messenger RNA levels of proliferation-related genes were measured using real-time PCR. The expression levels of Igf1, Lifr, Pdgfra, Bcl2, Ccnd3 and Pcna were upregulated by MENT, and those of Pdgfra, Ccnd3 and Pcna were upregulated by LH. Both LH and MENT stimulated the differentiation of progenitor Leydig cells in vitro. We concluded that both LH and MENT were involved in regulating the development of progenitor Leydig cells.

  11. Effects of exposure to male goat hair extracts on luteinizing hormone secretion and neuronal activation in seasonally anestrous ewes.

    PubMed

    Ohara, Hiromi; Mogi, Kazutaka; Ichimaru, Toru; Ohkura, Satoshi; Takeuchi, Yukari; Mori, Yuji; Okamura, Hiroaki

    2014-10-01

    In sheep and goats, exposure of seasonally anestrous females to males or their fleece/hair activates the gonadotropin-releasing hormone (GnRH) pulse generator leading to pulsatile luteinizing hormone (LH) secretion. Pheromones emitted by sexually mature males are thought to play a prominent role in this male effect. In the present study, we first aimed to clarify whether the male goat pheromone is effective in ewes. Seasonally anestrous St. Croix ewes were exposed to hair extracts derived from either intact or castrated (control) male Shiba goats. The male goat-hair extract significantly increased LH secretion compared to the control, suggesting that an interspecies action of the male pheromone occurs between sheep and goats. Using the male goat-hair extract as the pheromone source, we then aimed to clarify the neural pathway involved in the signal transduction of the male pheromone. Ewes were exposed to either the goat-hair extract or the control and sacrificed 2 hr after the exposure. Expression of c-Fos, a marker of neuronal activation, was immunohistochemically examined. The male goat-hair extract significantly increased the c-Fos expression compared to the control in regions of the vomeronasal system, such as the accessory olfactory bulb and medial amygdala, and the arcuate nucleus. The main olfactory bulb did not exhibit any significant increase in the c-Fos expression by the male goat-hair extract. This result suggests that the neural signal of the male pheromone is conveyed to the GnRH pulse generator through the activated regions in ewes.

  12. Immunoreactive luteinizing hormone, estradiol, progesterone, testosterone, and androstenedione levels during the breeding season and anestrus in Siberian tigers.

    PubMed

    Seal, U S; Plotka, E D; Smith, J D; Wright, F H; Reindl, N J; Taylor, R S; Seal, M F

    1985-03-01

    Seasonal analysis of 1239 captive births of Siberian tigers (Panthera tigris altaica) indicated a peak in April to June (P less than 0.001). Studies on seven animals in Minnesota indicated that behavioral heat cycles and ovarian follicular phase cycles began in late January and ceased in early June. Behavioral observation of 12 heat cycles in four tigers yielded an estrous length of 5.3 +/- 0.2 days and an interestrous interval of 25.0 +/- 1.3 days. Hormone assays on weekly blood samples (N = 180) from three female tigers indicated 16 cycles in two breeding seasons. Peak estradiol-17 beta levels were 46.7 +/- 6.0 pg/ml (N = 17) and interestrous concentrations were 8.7 +/- 0.66 pg/ml (N = 28) during the breeding season. Anestrous estradiol levels were 4.2 +/- 0.5 pg/ml (N = 70). The interestrous interval between estradiol peaks was 24.9 +/- 1.3 days (N = 9) with two outliers of 42 days. Serum progesterone concentrations from February to June were 1.2 +/- 0.15 ng/ml (N = 32), providing no evidence for ovulation or corpus luteum formation. Luteinizing hormone (LH) levels were 0.56 +/- 0.04 ng/ml (N = 180). Serum testosterone (r=0.71, P less than 0.001) and androstenedione levels (r=0.75, P less than 0.001) were correlated with estradiol during the breeding season. The duration of anestrus was 8 mo in two of these tigers. The interval was shortened in one tiger by exposure to a 16L:8D photoperiod. The Siberian tiger appears to be a polyestrous seasonal breeder and an induced ovulator whose breeding season may be synchronized by photoperiod.

  13. Altered regulation of luteinizing hormone secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats

    SciTech Connect

    Bookstaff, R.C.

    1989-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) severely decreases plasma androgen concentrations, yet plasma luteinizing hormone (LH) concentrations remain unchanged. The mechanism by which TCDD prevents the expected compensatory increase in plasma LH was investigated. No effect on the plasma disappearance rate of LH or on pituitary capacity to synthesize or secrete LH was detected. Rather, TCDD altered the regulation of LH secretion by substantially increasing the potency of both androgens and estrogens as feedback inhibitors of LH secretion. The mechanism by which TCDD alters androgen-regulated LH secretion was further investigated. Seven days after dosing, TCDD decreased plasma testosterone concentrations but prevented the expected compensatory increases in pituitary gonadotropin-releasing hormone (GnRH) receptor number, pituitary responsiveness to GnRH, and plasma LH concentrations as seen in similarly hypoandrogenic vehicle dosed rats. Furthermore, the TCDD dose-response relationships for preventing the compensatory increases in pituitary GnRH receptor number and plasma LH concentration were similar. However, in the absence of gonadal steroids (7 days after castration) TCDD did not affect the compensatory increases in pituitary GnRH receptor number, pituitary responsiveness to GnRH, or plasma LH concentration. All of these parameters increased substantially relative to intact TCDD treated rats, and to levels virtually identical to those seen in castrated control rats. Treatment of castrated rats with testosterone restored the ability of TCDD to prevent these compensatory increases. Taken together, these results demonstrate that the presence of androgens is required for TCDD to alter the regulation of pituitary GnRH receptors.

  14. A novel monoclonal antibody-based enzyme-linked immunosorbent assay to determine luteinizing hormone in bovine plasma.

    PubMed

    Borromeo, V; Berrini, A; De Grandi, F; Cremonesi, F; Fiandanese, N; Pocar, P; Secchi, C

    2014-07-01

    The development of a novel enzyme-linked immunosorbent assay (ELISA) for determining luteinizing hormone (LH) in bovine plasma is described. Anti-bovine LH (bLH) monoclonal antibodies (mAbs) were produced and characterized. One mAb recognizing the bLH β subunit was used for immunoaffinity purification of substantial amounts of biologically active bLH from pituitary glands. The purified bLH in combination with 2 anti-bLH β subunit mAbs was used to develop a sandwich ELISA, which satisfied all the criteria required to investigate LH secretory patterns in the bovine species. The ELISA standard curve was linear over the range 0.05 to 2.5 ng/mL, and the assay proved suitable for measuring bLH in plasma without any prior treatment of samples. Cross-reactivity and recovery tests confirmed the specificity of the method. The intra- and inter-assay coefficients of variation ranged between 3.41% and 9.40%, and 9.29% and 15.84%, respectively. The analytical specificity of the method was validated in vivo by provocative tests for LH in heifers, using the LH releasing peptide gonadotropin-releasing hormone. In conclusion, the adoption of mAbs for this ELISA for coating the wells and labeling, combined with the easy one-step production of reference bLH, ensures long-term continuity in large-scale measurements of LH in the bovine species. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Use of porcine luteinizing hormone at oestrous onset in a protocol for fixed-time artificial insemination in gilts.

    PubMed

    Ulguim, R R; Fontana, D L; Rampi, J Z; Bernardi, M L; Wentz, I; Bortolozzo, F P

    2014-10-01

    The aim of this study was to evaluate the effect of porcine luteinizing hormone (pLH) given at oestrous onset in gilts, by different routes and doses, on the interval between onset of oestrus and ovulation (IOEO) and reproductive performance using a single fixed-time artificial insemination (FTAI). A total of 153 gilts were submitted to oestrous detection at 8-h intervals and assigned to three groups: control - without hormone application and inseminated at 0, 24 and 48 h after oestrous onset; VS2.5FTAI - 2.5 mg pLH by the vulvar submucosal route at oestrous onset and a single FTAI 16 h later; IM5FTAI - 5 mg pLH by the intramuscular route at oestrous onset and a single FTAI 16 h later. More VS2.5FTAI gilts (47.1%; p < 0.05) ovulated within 24 h after oestrous onset than control gilts (25.5%) whereas IM5FTAI gilts had an intermediate percentage (31.4%; p > 0.05). The IOEO tended to be shorter (p = 0.06) in VS2.5FTAI (30.2 ± 1.4 h) than in control (34.7 ± 1.4 h) gilts, but there was no difference (p > 0.05) between control and IM5FTAI (32.8 ± 1.4 h) gilts. Farrowing rate was not different (p > 0.05) among treatments. Total born piglets (TB) was lower (p < 0.05) in VS2.5FTAI (12.3 ± 0.4) than in control gilts (14.1 ± 0.4), whereas intermediate TB was observed in IM5FTAI gilts (13.3 ± 0.4). Due to the advancement of ovulation, reduction of the hormonal dose and the ease of application, the vulvar submucosal route would be the best option for FTAI protocols, but their negative impact on litter size remains to be elucidated. Taking into account the good fertility results obtained in IM5FTAI gilts whose ovulation was not advanced, the possibility of a single FTAI without any hormonal treatment should be further investigated, to establish reliable FTAI protocols for gilts.

  16. Random unstimulated pediatric luteinizing hormone levels are not reliable in the assessment of pubertal suppression during histrelin implant therapy

    PubMed Central

    2013-01-01

    Background Gonadotropin-releasing hormone agonist (GnRHa)-stimulated luteinizing hormone (LH) is the standard hormonal assessment for both diagnosis and therapeutic monitoring of children with central precocious puberty (CPP). Use of unstimulated (random) LH levels may be helpful in diagnosis and has gained popularity in monitoring GnRHa therapy despite lack of validation against stimulated values. The objective of this investigation was to assess the suitability of random LH for monitoring pubertal suppression during GnRHa treatment. Methods Data from a multi-year, multicenter, open-label trial of annual histrelin implants for CPP was used for our analysis. Children meeting clinical and hormonal criteria for CPP, either naïve to GnRHa therapy or previously treated with another GnRHa for at least 6 months who were being treated at academic pediatric centers were included in the study. Subjects received a single 50-mg subcutaneous histrelin implant annually until final explant at an age determined at the discretion of each investigator. Monitoring visits for physical examination and GnRHa-stimulation testing were performed at regular intervals. The main outcome measure was pubertal suppression during treatment defined by peak LH < 4 mIU/mL after GnRHa stimulation. Results During histrelin treatment, 36 children underwent a total of 308 monitoring GnRHa stimulation tests. Unstimulated and peak LH levels were positively correlated (r = 0.798), and both declined from the first to second year of treatment. Mean ± SD peak LH level during therapy was 0.62 ± 0.43 mIU/mL (range, 0.06–2.3), well below the normal prepubertal mean. Mean random LH was 0.35 ± 0.25 mIU/mL (range, 0.04–1.5), 10-fold higher than the normal prepubertal mean. The random LH levels were above the prepubertal upper threshold (<0.3 mIU/mL) in 48.4% of all tests and in 88.9% of subjects at some point during therapy. Conclusions In contrast with GnRHa-stimulated LH

  17. Older males secrete luteinizing hormone and testosterone more irregularly, and jointly more asynchronously, than younger males

    PubMed Central

    Pincus, Steven M.; Mulligan, Thomas; Iranmanesh, Ali; Gheorghiu, Sylvia; Godschalk, Michael; Veldhuis, Johannes D.

    1996-01-01

    New statistical perspectives on the secretory patterns of both luteinizing hormone (LH) and testosterone (T) may prove useful in further understanding the aging process, and possibly ultimately in improving the diagnosis and treatment of spermatogenetic failure and loss of sexual interest. We examined serum concentration time-series for LH and T in 14 young (21–34 years of age) and 11 aged (62–74 years of age) healthy men. For each subject, blood samples were obtained at 2.5-min intervals during a sleep period, with an average sampling duration of 7 hr. For each of LH and T, we used the model-independent statistic approximate entropy (ApEn) to quantify the irregularity of the serum concentration time-series; to quantify joint LH–T secretory asynchrony, we employed the recently introduced cross-ApEn. Although mean (and SD) LH and T concentrations were indistinguishable in the two age groups (P > 0.25), for LH, aged subjects had greater ApEn values (1.525 ± 0.221) than younger individuals (1.207 ± 0.252), P < 0.003, indicating more irregular secretion in the older cohort. For T, aged subjects also had greater ApEn values (1.622 ± 0.120) than younger counterparts (1.384 ± 0.228), P < 0.004. In young, but not older men, ApEn(T) significantly exceeded ApEn(LH), P < 0.02. Aged subjects had greater cross-ApEn values (1.961 ± 0.121) than younger subjects (1.574 ± 0.249), P < 10−4, with nearly 100% sensitivity and specificity, indicating greater LH–T asynchrony in the older group. In conjunction with previous findings of greater irregularity of growth hormone release with increasing age, we propose that increased secretory irregularity with advancing age may be a widespread hormonal phenomenon. Finally, theoretically, we clarify the need for quantifications such as ApEn and cross-ApEn via a study of a “variable lag” pulsatile process, and empirically note the potential wide applicability of cross-ApEn to quantify asynchrony in interconnected (hormonal

  18. Uncoupling protein-3 is a molecular determinant for the regulation of resting metabolic rate by thyroid hormone.

    PubMed

    de Lange, P; Lanni, A; Beneduce, L; Moreno, M; Lombardi, A; Silvestri, E; Goglia, F

    2001-08-01

    Thyroid hormones increase energy expenditure, partly by reducing metabolic efficiency. The control of specific genes at the transcriptional level is thought to be the major molecular mechanism. However, both the number and the identity of the thyroid hormone-controlled genes remain unknown, as do their relative contributions. Uncoupling protein-3, a recently identified member of the mitochondrial transporter superfamily and one that is predominantly expressed in skeletal muscle, has the potential to be a molecular determinant for thyroid thermogenesis. However, changes in mitochondrial proton conductance and resting metabolic rate after physiologically mediated changes in uncoupling protein-3 levels have not been described. Here, in a study on hypothyroid rats given a single injection of T(3), we describe a strict correlation in terms of time course between the induced increase in uncoupling protein-3 expression (at mRNA and protein levels) and decrease in mitochondrial respiratory efficiency, on the one hand, and the increase in resting metabolic rate, on the other. First, we describe our finding that uncoupling protein-3 is present and regulated by T(3) only in metabolically relevant tissues (such as skeletal muscle and heart). Second, we follow the time course (at 0, 6, 12, 24, 48, 65, 96, and 144 h) of both uncoupling protein-3 mRNA levels and mitochondrial uncoupling protein-3 density in gastrocnemius muscle and heart. In both tissues, the maximal (12-fold) increase in uncoupling protein-3 density was reached at 65 h. The resting metabolic rate [lO(2)(kg(0.75))(-1)h(-1)] showed the same time course, and at 65 h the increase vs. time zero was 45% (1.316 +/- 0.026 vs. 0.940 +/- 0.007; P < 0.001). At the same time point, gastrocnemius muscle mitochondria showed a significantly higher nonphosphorylating respiration rate (nanoatoms of oxygen per min/mg protein; increase vs. time zero, 40%; 118 +/- 4 vs. 85 +/- 9; P < 0.05), whereas the membrane potential decreased

  19. A comparison of human chorionic gonadotropin and luteinizing hormone releasing hormone on the induction of spermiation and amplexus in the American toad (Anaxyrus americanus)

    PubMed Central

    2012-01-01

    Background Captive breeding programs for endangered amphibian species often utilize exogenous hormones for species that are difficult to breed. The purpose of our study was to compare the efficacy of two different hormones at various concentrations on sperm production, quantity and quality over time in order to optimize assisted breeding. Methods Male American toads (Anaxyrus americanus) were divided into three separate treatment groups, with animals in each group rotated through different concentrations of luteinizing hormone releasing hormone analog (LHRH; 0.1, 1.0, 4.0 and 32 micrograms/toad), human chorionic gonadotropin (hCG; 50, 100, 200, and 300 IU), or the control over 24 hours. We evaluated the number of males that respond by producing spermic urine, the sperm concentration, percent motility, and quality of forward progression. We also evaluated the effects of hCG and LHRH on reproductive behavior as assessed by amplexus. Data were analyzed using the Generalized Estimating Equations incorporating repeated measures over time and including the main effects of treatment and time, and the treatment by time interaction. Results The hormone hCG was significantly more effective at stimulating spermiation in male Anaxyrus americanus than LHRH and showed a dose-dependent response in the number of animals producing sperm. At the most effective hCG dose (300 IU), 100% of the male toads produced sperm, compared to only 35% for the best LHRH dose tested (4.0 micrograms). In addition to having a greater number of responders (P < 0.05), the 300 IU hCG treatment group had a much higher average sperm concentration (P < 0.05) than the treatment group receiving 4.0 micrograms LHRH. In contrast, these two treatments did not result in significant differences in sperm motility or quality of forward progressive motility. However, more males went into amplexus when treated with LHRH vs. hCG (90% vs. 75%) by nine hours post-administration. Conclusion There is a clear

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

    SciTech Connect

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

    2010-04-15

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

  1. Inhibition of growth of OV-1063 human epithelial ovarian cancer xenografts in nude mice by treatment with luteinizing hormone-releasing hormone antagonist SB-75.

    PubMed Central

    Yano, T; Pinski, J; Halmos, G; Szepeshazi, K; Groot, K; Schally, A V

    1994-01-01

    Female athymic nude mice bearing xenografts of OV-1063 human epithelial ovarian cancer cell line were treated with potent luteinizing hormone (LH)-releasing hormone (LH-RH) antagonist SB-75 (Cetrorelix; [Ac-D-Nal(2)1, D-Phe(4 CI)2, D-Pal(3)3, D-Cit6, D-Ala10]LH-RH in which Ac-D-Nal(2) = N-acetyl-3-(2-naphthyl)-D-alanine, D-Phe(4CI) = 4-chloro-D-phenylalanine, D-Pal(3) = 3-(3-pyridyl)-D-alanine, and D-Cit = D-Citrulline) or with the agonist [D-Trp6]LH-RH. In the first experiment, SB-75 and [D-Trp6]LH-RH were administered in the form of microcapsules releasing 60 and 25 micrograms/day, respectively. In the second study, the analogs were given by daily s.c. injections in doses of 100 micrograms/day. In both experiments, tumor growth, as measured by reduction in tumor volume, percentage change in tumor volume, tumor burden, and increase in tumor doubling time, was significantly inhibited by treatment with SB-75 but not with [D-Trp6]LH-RH. Uterine and ovarian weights were reduced and serum LH levels decreased by administration of either analog. Chronic treatment with SB-75 greatly reduced the concentration of receptors for epidermal growth factor and insulin-like growth factor I in tumor cell membranes, a phenomenon that might be related to tumor growth inhibition. It is possible that the antitumoral effects of SB-75 on OV-1063 ovarian cancers are exerted not only through the suppression of the pituitary-gonadal axis, but also directly. In view of its strong inhibitory effect on the growth of OV-1063 ovarian cancers in vivo, the potent LH-RH antagonist SB-75 might be considered for possible hormonal therapy of advanced epithelial ovarian carcinoma. PMID:7518926

  2. Role of estradiol in cortisol-induced reduction of luteinizing hormone pulse frequency.

    PubMed

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

    2009-06-01

    Precise control of pulsatile GnRH and LH release is imperative to ovarian cyclicity but is vulnerable to environmental perturbations, like stress. In sheep, a sustained (29 h) increase in plasma cortisol to a level observed during stress profoundly reduces GnRH pulse frequency in ovariectomized ewes treated with ovarian steroids, whereas shorter infusion (6 h) is ineffective in the absence of ovarian hormones. This study first determined whether the ovarian steroid milieu or duration of exposure is the relevant factor in determining whether cortisol reduces LH pulse frequency. Prolonged (29 h) cortisol infusion did not lower LH pulse frequency in ovariectomized ewes deprived of ovarian hormones, but it did so in ovariectomized ewes treated with estradiol and progesterone to create an artificial estrous cycle, implicating ovarian steroids as the critical factor. Importantly, this effect of cortisol was more pronounced after the simulated preovulatory estradiol rise of the artificial follicular phase. The second experiment examined which component of the ovarian steroid milieu enables cortisol to reduce LH pulse frequency in the artificial follicular phase: prior exposure to progesterone in the luteal phase, low early follicular phase estradiol levels, or the preovulatory estradiol rise. Basal estradiol enabled cortisol to decrease LH pulse frequency, but the response was potentiated by the estradiol rise. These findings lead to the conclusion that ovarian steroids, particularly estradiol, enable cortisol to inhibit LH pulse frequency. Moreover, the results provide new insight into the means by which gonadal steroids, and possibly reproductive status, modulate neuroendocrine responses to stress.

  3. 'Carriers of variant luteinizing hormone (V-LH) among 1593 Baltic men have significantly higher serum LH'.

    PubMed

    Punab, A M; Grigorova, M; Punab, M; Adler, M; Kuura, T; Poolamets, O; Vihljajev, V; Žilaitienė, B; Erenpreiss, J; Matulevičius, V; Laan, M

    2015-05-01

    Luteinizing hormone (LH) is a pituitary heterodimeric glycoprotein essential in male and female reproduction. Its functional polymorphic variant (V-LH) is determined by two missense mutations (rs1800447, A/G, Trp8Arg; rs34349826, A/G, Ile15Thr) in the LH β-subunit encoding gene (LHB; 19q13.3; 1111 bp; 3 exons). Among women, V-LH has been associated with higher circulating LH and reduced fertility, but the knowledge of its effect on male reproductive parameters has been inconclusive. The objective of this study was to assess the effect of V-LH on hormonal, seminal and testicular parameters in the Baltic young men cohort (n = 986; age: 20.1 ± 2.1 years) and Estonian idiopathic infertility patients (n = 607; 35.1 ± 5.9 years). V-LH was detected by genotyping of the underlying DNA polymorphisms using PCR-RFLP combined with resequencing of a random subset of subjects. Genetic associations were tested using linear regression under additive model and results were combined in meta-analysis. No significant difference was detected between young men and infertility patients for the V-LH allele frequency (11.0 vs. 9.3%, respectively). V-LH was associated with higher serum LH in both, the young men cohort (p = 0.022, allelic effect = 0.26 IU/L) and the idiopathic infertility group (p = 0.008, effect = 0.59 IU/L). In meta-analysis, the statistical significance was enhanced (p = 0.0007, resistant to Bonferroni correction for multiple testing; effect = 0.33 IU/L). The detected significant association of V-LH with increased serum LH remained unchanged after additional adjustment for the SNPs previously demonstrated to affect LH levels (FSHB -211G/T, FSHR Asn680Ser, FSHR -29A/G). Additionally, a suggestive trend for association with reduced testicular volume was observed among young men, and with lower serum FSH among infertility patients. The V-LH carrier status did not affect sperm parameters and other circulating reproductive hormones. For the first time, we show a conclusive

  4. Combination of a long-acting delivery system for luteinizing hormone-releasing hormone agonist with Novantrone chemotherapy: increased efficacy in the rat prostate cancer model.

    PubMed Central

    Schally, A V; Kook, A I; Monje, E; Redding, T W; Paz-Bouza, J I

    1986-01-01

    The combination of hormonal treatment based on a long-acting delivery system for the agonist [6-D-tryptophan]luteinizing hormone-releasing hormone ([D-Trp6]-LH-RH) with the chemotherapeutic agent Novantrone (mitoxantrone dihydrochloride) was studied in the Dunning R3327H rat prostate cancer model. Microcapsules of [D-Trp6]-LH-RH formulated from poly(DL-lactide-co-glycolide) and calculated to release a controlled dose of 25 micrograms/day were injected intramuscularly once a month. Novantrone (0.25 mg/kg) was injected intravenously once every 3 weeks. Three separate experiments were carried out. When the therapy was started 45 days after transplantation and continued for 70 days, tumor volume in the presence of the microcapsules (966 +/- 219 mm3) or Novantrone (3606 +/- 785 mm3) given alone was significantly decreased compared to controls (14,476 +/- 3045 mm3). However, the combination of microcapsules and Novantrone caused a greater inhibition of tumor growth (189 +/- 31 mm3) than the single agents. Similar effects were seen when the percent increase in tumor volume was examined. Tumor volume increased 10,527 +/- 1803% for the control group. The inhibition of growth caused by the [D-Trp6]LH-RH microcapsules alone (672 +/- 153% increase in volume) was again greater than that caused by Novantrone alone (2722 +/- 421% increase). The combination of the two agents was again the most effective, resulting in an increase in tumor volume of only 105 +/- 29%. Control tumors weighed 30.0 +/- 6.5 g. Tumor weights were much less in the groups treated with either microcapsules (3.28 +/- 0.69 g) or Novantrone (19.53 +/- 3.3 g) alone. The lowest tumor weights after 70 days of treatment were obtained in the group that received the combination of [D-Trp6]LH-RH microcapsules and Novantrone (1.02 +/- 0.2 g). Testes and ventral prostate weights were significantly diminished by the administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Novantrone. In both of these

  5. Effect of rabbit doe-litter separation on 24-hour changes of luteinizing hormone, follicle stimulating hormone and prolactin release in female and male suckling pups

    PubMed Central

    Cano, Pilar; Jiménez-Ortega, Vanesa; P Álvarez, Maria; Alvariño, Mario; Cardinali, Daniel P; Esquifino, Ana I

    2005-01-01

    Background The daily pattern of nursing of the rabbit pup by the doe is the most important event in the day for the newborn and is neatly anticipated by them. Such anticipation presumably needs a close correlation with changes in hormones that will allow the pups to develop an appropriate behavior. Although a number of circadian functions have been examined in newborn rabbits, there is no information on 24-h pattern of gonadotropin release or on possible sex-related differences in gonadotropin or prolactin (PRL) release of pups. This study examined the 24-h changes of plasma luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) in 11 days old suckling female and male rabbits left with the mother or after short-term (i.e., 48 h) doe-litter separation. Methods Animals were kept under controlled light-dark cycles (16 h – 8 h; lights on at 08:00 h). On day 9 post partum, groups of 6–7 female or male rabbit pups were separated from their mothers starting at 6 different time intervals in the 24 h cycle. Pups were killed 48 h after separation. At each time interval groups of male or female pups that stayed with the mother were killed as controls. Plasma, LH, FSH and PRL levels were measured by specific radioimmunoassays. Results In pups kept with their mother plasma FSH and LH maxima occurred at the first and second part of the light phase (at 13:00 and 17:00 – 21:00 h, respectively) (females) or as two peaks for each of the hormones (at 13:00 and 01:00 h) (males). PRL release was similar in female and male rabbit pups kept with their mother, showing a 24-h pattern with two peaks, at 13:00 and 01:00 h, respectively. Mean 24-h values of gonadotropins and PRL did not differ between sexes. Isolation of pups for 48 h augmented circulating gonadotropin and PRL levels and distorted hormone 24-h pattern to a similar extent in both sexes. Conclusion Significant sex differences in 24-h changes in LH and FSH, but not in PRL, release occurred in

  6. Is the growth outcome of children with idiopathic short stature and isolated growth hormone deficiency following treatment with growth hormone and a luteinizing hormone-releasing hormone agonist superior to that obtained by GH alone?

    PubMed

    Colmenares, Ana; González, Laura; Gunczler, Peter; Lanes, Roberto

    2012-01-01

    The aim of this study was to evaluate the effect of combined therapy with growth hormone (GH) and luteinizing hormone-releasing hormone agonist (LHRHa) on the near-final height (NFH) of children with idiopathic short stature (ISS) and growth hormone deficiency (GHD) in early puberty. A retrospective analysis of 20 patients with ISS and 9 patients with GHD treated with combined therapy was undertaken. Twelve children with ISS and ten with GHD, treated with GH alone, served as controls. Patients were matched at baseline for chronological age, bone age, height standard deviation score (SDS), and pubertal development. Patients with ISS or GHD treated with combined therapy improved both their predicted adult height (PAH) at 2 years of therapy (ISS, p < 0.001; GHD, p = 0.03) and their NFH (ISS, p < 0.05; GHD, p = 0.05). Treatment with combined therapy did not generate additional benefits on the PAH after 2 years of therapy (ISS children, an increase of 7.9 +/- 4.9 cm with combined therapy vs. 7.3 +/- 6.0 cm with GH; GHD children, an increase of 6.8 +/- 7.8 cm with combined therapy vs. 5 +/- 5.9 cm with GH). The total height gain SDS was higher in patients treated with GH alone compared with those with combined therapy, but the difference was not significant (ISS children, a gain of 2.4 SDS with GH vs. 0.8 SDS with combined therapy; GHD children, a gain of 1.8 SDS with GH vs. 0.6 SDS with combined therapy). Although 2 years of combined treatment with GH and LHRHa improved the PAH and the NFH of ISS and GHD patients in early puberty, this improvement was not significant compared with that observed in similar subjects treated with GH alone.

  7. Efficacy and safety of luteinizing hormone-releasing hormone antagonist cetrorelix in the treatment of symptomatic benign prostatic hyperplasia.

    PubMed

    Comaru-Schally, A M; Brannan, W; Schally, A V; Colcolough, M; Monga, M

    1998-11-01

    As the life expectancy for men increases, more cases of benign prostatic hyperplasia (BPH) will be expected. Symptomatic BPH causes morbidity and can lower the quality of life. We investigated whether short term administration of the LH-releasing hormone antagonist cetrorelix could provide an improved treatment for men with BPH. Thirteen patients with moderate to severe symptomatic BPH were treated with cetrorelix (5 mg, s.c., twice daily for 2 days followed by 1 mg/day, s.c., for 2 months). Patients were evaluated at baseline, during treatment, and up to 18 months after therapy. We determined the effects of cetrorelix on the International Prostate Symptom Score (IPSS), Quality of Life score, sexual function, prostate size, uroflowmetry, and hormonal levels. Treatment with cetrorelix produced a decline of 52.9% (P < 0.0001) in IPSS, a 46% improvement in the Quality of Life score (P < 0.001), a rapid reduction of 27% (P < 0.006) in prostatic volume, and an increase in peak urinary flow rates by 2.86 mL/s. Serum testosterone fell to castrate levels on day 2, but was inhibited only by 64-74% during maintenance therapy, and after cessation of treatment returned to normal. During long term follow-up, most patients continued to show a progressive improvement in urinary symptoms (decline in IPSS from 67% to 72% at weeks 20 and 85, respectively) and an enhancement of sexual function, and prostatic volume remained normal. Our study demonstrates that in patients with symptomatic BPH, treatment with cetrorelix is safe and produces long term improvement.

  8. Luteal Phase Dynamics of Follicle Stimulating and Luteinizing Hormones in Obese and Normal Weight Women

    PubMed Central

    Roth, Lauren W.; Allshouse, Amanda A.; Bradshaw-Pierce, Erica L.; Lesh, Jennifer; Chosich, Justin; Kohrt, Wendy; Bradford, Andrew P.; Polotsky, Alex J.; Santoro, Nanette

    2014-01-01

    Summary Objectives Female obesity is a state of relative hypogonadotrophic hypogonadism. The aim of this study is to examine gonadotrophin secretion and response to GnRH in the luteal phase of the menstrual cycle and to investigate the pharmacodynamics and pharmacokinetics of endogenous and exogenous LH in obese women. Design Participants underwent a luteal phase frequent blood sampling study. Endogenous LH pulsatility was observed, gonadotrophin releasing hormone (GnRH) was given in 2 weight based doses, and GnRH antagonist was administered followed by recombinant LH. Patients Regularly menstruating obese (n=10) and normal weight (n=10) women Measurements Endogenous hypothalamic-pituitary function (as measured by LH pulsatility), pituitary sensitivity (GnRH induced LH secretion), pharmacodynamics of endogenous LH, and pharmacokinetics of exogenous LH were compared between the obese and normal weight groups. Results There were no statistically significant differences in endogenous LH pulsatility or pituitary responses to two weight-based doses of GnRH between the obese and normal weight women. There were no differences in the pharmacodynamics of endogenous LH or the pharmacokinetics of exogenous LH between the groups. FSH dynamics did not differ between the groups throughout the study. Conclusions The relative hypogonadotrophic hypogonadism of obesity cannot be explained by differences in LH and FSH luteal phase dynamics or differences in endogenous LH pharmacodynamics or exogenous LH pharmacokinetics. Clinical trial registration number NCT01457703, www.clinicaltrials.gov PMID:24576183

  9. Multiple Pathways Mediate Luteinizing Hormone Regulation of cGMP Signaling in the Mouse Ovarian Follicle1

    PubMed Central

    Liu, Xueqing; Xie, Fang; Zamah, Alberuni Musa; Cao, Binyun; Conti, Marco

    2014-01-01

    ABSTRACT Luteinizing hormone (LH) regulation of the epidermal growth factor (EGF) network is critical for oocyte maturation and the ovulatory process. Recent studies have indicated that C-type natriuretic peptide (CNP) and its receptor natriuretic peptide receptor B (NPR2) play an important role in the control of meiotic arrest. Here, we investigated the involvement of the EGF network in the LH-dependent regulation of the CNP/NPR2 axis and cGMP accumulation. LH/hCG treatment causes a major decrease in both cGMP and the CNP precursor (natriuretic peptide precursor C [Nppc]) mRNA accumulation in vivo and in vitro. However, the cGMP downregulation precedes the decrease in Nppc mRNA by more than 1 h. Amphiregulin, an EGF-like factor, suppresses Nppc mRNA levels in cultured follicles to the same extent as LH, and this effect is completely prevented by the EGF receptor (EGFR) kinase inhibitor AG1478. However, the LH-dependent suppression of Nppc is insensitive to AG1478. Similarly, Nppc suppression by LH occurs in follicles from EGFR null mice. These findings document that EGFR signaling is sufficient to downregulate CNP, but is not necessary for LH action. When cGMP concentration in the follicle is measured, the short-term, but not long-term, LH effects on cGMP are prevented by AG1478, suggesting that ligand availability may be responsible for the late response. Human CG decreases the CNP-dependent cGMP synthesis in wild-type and EGFR knockdown cumulus-oocyte complexes. These findings demonstrate that redundant pathways are involved in the regulation of cGMP. EGFR-dependent events are involved in the short-term regulation of cGMP, whereas the long-term effects may involve regulation of the CNP. PMID:24740605

  10. Variation in levels of luteinizing hormone and reproductive photoresponsiveness in a population of white-footed mice (Peromyscus leucopus)

    PubMed Central

    Pittman, Julian T.; Schubert, Kristin A.; Dubois, Christen M. R.; Bowles, Jennifer; Lowe, Sean M.; Price, Matthew R.

    2010-01-01

    Natural genetic variation in reproduction and life history strategies is a manifestation of variation in underlying regulatory neuronal and endocrine systems. A test of the hypothesis that genetic variation in luteinizing hormone (LH) level could be related to a life history trait, seasonal reproduction, was conducted on artificial selection lines from a wild-source population of white-footed mice (Peromyscus leucopus). Variation exists in the degree of suppression of reproduction by winter short-day photoperiods (SD) in wild-source individuals and in the laboratory population. In this population, most individuals from a photoperiod-responsive (R) artificial selection line are strongly suppressed reproductively in SD, while most individuals from a photoperiod-nonresponsive (NR) artificial selection line are only weakly reproductively suppressed in SD. We assayed levels of LH to test for genetic variation between lines that could contribute to variation in reproductive status in SD. Females from both lines were raised in long-day photoperiods (LD) or SD, ovariectomized under isoflurane anesthesia, and given estradiol implants. Levels of LH were significantly higher in the NR line than in the R line, indicating genetic variation for levels of LH. Levels of LH were higher in LD than in SD, indicating that levels of LH were sensitive to photoperiod treatment even with a controlled level of estradiol negative feedback. The results indicate that there is genetic variation in levels of LH that could be functionally important both in the laboratory in SD and in the wild population in winter. Thus genetic variation in levels of LH is a plausible causal factor determining winter reproductive phenotype in the wild population. PMID:20357020

  11. Variation in levels of luteinizing hormone and reproductive photoresponsiveness in a population of white-footed mice (Peromyscus leucopus).

    PubMed

    Heideman, Paul D; Pittman, Julian T; Schubert, Kristin A; Dubois, Christen M R; Bowles, Jennifer; Lowe, Sean M; Price, Matthew R

    2010-06-01

    Natural genetic variation in reproduction and life history strategies is a manifestation of variation in underlying regulatory neuronal and endocrine systems. A test of the hypothesis that genetic variation in luteinizing hormone (LH) level could be related to a life history trait, seasonal reproduction, was conducted on artificial selection lines from a wild-source population of white-footed mice (Peromyscus leucopus). Variation exists in the degree of suppression of reproduction by winter short-day photoperiods (SD) in wild-source individuals and in the laboratory population. In this population, most individuals from a photoperiod-responsive (R) artificial selection line are strongly suppressed reproductively in SD, while most individuals from a photoperiod-nonresponsive (NR) artificial selection line are only weakly reproductively suppressed in SD. We assayed levels of LH to test for genetic variation between lines that could contribute to variation in reproductive status in SD. Females from both lines were raised in long-day photoperiods (LD) or SD, ovariectomized under isoflurane anesthesia, and given estradiol implants. Levels of LH were significantly higher in the NR line than in the R line, indicating genetic variation for levels of LH. Levels of LH were higher in LD than in SD, indicating that levels of LH were sensitive to photoperiod treatment even with a controlled level of estradiol negative feedback. The results indicate that there is genetic variation in levels of LH that could be functionally important both in the laboratory in SD and in the wild population in winter. Thus genetic variation in levels of LH is a plausible causal factor determining winter reproductive phenotype in the wild population.

  12. Luteinizing Hormone-Induced RUNX1 Regulates the Expression of Genes in Granulosa Cells of Rat Periovulatory Follicles

    PubMed Central

    Jo, Misung; Curry, Thomas E.

    2006-01-01

    The LH surge induces specific transcription factors that regulate the expression of a myriad of genes in periovulatory follicles to bring about ovulation and luteinization. The present study determined 1) the localization of RUNX1, a nuclear transcription factor, 2) regulation of Runx1 mRNA expression, and 3) its potential function in rat ovaries. Up-regulation of mRNA and protein for RUNX1 is detected in preovulatory follicles after human chorionic gonadotropin (hCG) injection in gonadotropin-treated immature rats as well as after the LH surge in cycling animals by in situ hybridization and immunohistochemical and Western blot analyses. The regulation of Runx1 mRNA expression was investigated in vitro using granulosa cells from rat pre-ovulatory ovaries. Treatments with hCG, forskolin, or phorbol 12 myristate 13-acetate stimulated Runx1 mRNA expression. The effects of hCG were reduced by inhibitors of protein kinase A, MAPK kinase, or p38 kinase, indicating that Runx1 expression is regulated by the LH-initiated activation of these signaling mediators. In addition, hCG-induced Runx1 mRNA expression was inhibited by a progesterone receptor antagonist and an epidermal growth factor receptor tyrosine kinase inhibitor, whereas amphiregulin stimulated Runx1 mRNA expression, demonstrating that the expression is mediated by the activation of the progesterone receptor and epidermal growth factor receptor. Finally, knockdown of Runx1 mRNA by small interfering RNA decreased progesterone secretion and reduced levels of mRNA for Cyp11a1, Hapln1, Mt1a, and Rgc32. The hormonally regulated expression of Runx1 in periovulatory follicles, its involvement in progesterone production, and regulation of preovulatory gene expression suggest important roles of RUNX1 in the periovulatory process. PMID:16675540

  13. Ovine luteinizing hormone. VI. Analysis of the misclassification errors in the separation of intrapituitary isohormones by chromatofocusing.

    PubMed

    Grotjan, H E; Zalesky, D D

    1991-07-19

    Luteinizing hormone (LH) in extracts of the ovine (o) anterior pituitary gland elutes as eight or more distinct peaks when analyzed by chromatofocusing on pH 10.5-7 gradients [Keel et al., Biol. Reprod., 36 (1987) 1102]. In order to examine the efficacy of this approach to identify the distinct charge isomers of oLH, a pool of pituitary extracts was de-salted by flow dialysis and chromatofocused on a pH 10.5-7 gradient. The immunoreactive oLH eluted in nine distinct peaks which were coded with letters beginning with the most basic form. The fractions corresponding to each peak were pooled, dialyzed and lyophilized. Each peak was then re-chromatofocused on a pH 10.5-7 gradient except for the immunoreactive oLH eluting in peak A' because of the small amount present in this peak. Each peak, except for F and H, also consisted of a small percentage of immunoreactive oLH associated with adjacent peaks. This was plausible because chromatofocusing does not generally yield baseline resolution of peaks. Peak H eluted in a broad manner and was contaminated with significant amounts of isohormones F, G and Z. In contrast, peaks B, E, F, G and Z almost completely eluted in the anticipated regions. Thus, it appears that analysis of oLH charge isomers by chromatofocusing yields minimal misclassification errors and that the misclassification errors observed are associated with molecular forms which comprise a relatively small percentage of the oLH in pituitary extracts.

  14. Decreased luteinizing hormone pulse frequency is associated with elevated 24-hour ghrelin after calorie restriction and exercise in premenopausal women

    PubMed Central

    Scheid, Jennifer L.; De Souza, Mary Jane; Hill, Brenna R.; Leidy, Heather J.

    2013-01-01

    Elevated ghrelin has been shown to be associated with reduced luteinizing hormone (LH) pulsatility in Rhesus monkeys, rats, men, and recently women. We previously reported that 24-h ghrelin concentrations are elevated in women following a 3-mo exercise and diet program leading to weight loss. We investigated whether the elevations in ghrelin following an ∼3-mo exercise and diet program leading to weight loss are associated with a decrease in LH pulsatility. The nonexercising control group (Control, n = 5) consumed a controlled diet that matched energy needs, whereas energy intake in the exercise group (Energy Deficit, n = 16) was reduced from baseline energy requirements and supervised exercise training occurred five times per a week. Significant decreases in body weight (−3.0 ± 0.6 kg), body fat (−2.9 ± 0.4 kg) and 24-h LH pulse frequency (−0.18 ± 0.08 pulses/h), and a significant increase in 24-h mean ghrelin were observed in only the Energy Deficit group. The pre-post change in LH pulse frequency was negatively correlated with the change in mean 24-h ghrelin (R = −0.485, P = 0.030) and the change in peak ghrelin at lunch (R = −0.518, P = 0.019). Interestingly, pre-post change in night LH pulse frequency was negatively correlated with the change in mean day ghrelin (R = −0.704, P = 0.001). Elevated total ghrelin concentrations are associated with the suppression of LH pulsatility in premenopausal women and may play a role in the suppression of reproductive function following weight loss. PMID:23115078

  15. INTERACTION BETWEEN GABA AND NOREPINEPHRINE IN INTERLEUKIN-1β-INDUCED SUPPRESSION OF THE LUTEINIZING HORMONE SURGE

    PubMed Central

    Sirivelu, Madhu P.; Burnett, Robert; Shin, Andrew C.; Kim, Charlotte; MohanKumar, P.S.; MohanKumar, Sheba M.J.

    2009-01-01

    Interleukin-1β (IL-1β), a cytokine that is closely associated with inflammation and immune stress, is known to interfere with reproductive functions. Earlier studies have demonstrated that IL-1β inhibits the luteinizing hormone (LH) surge during the afternoon of proestrus in female rats. We have shown that this effect is most probably mediated through a reduction in norepinephrine (NE) levels in the medial preoptic area (MPA) of the hypothalamus. However, the mechanism by which IL-1β decreases NE levels in the MPA is unclear. We hypothesized that the inhibitory neurotransmitter, GABA could play a role in decreasing NE levels in the MPA. To test this, ovariectomized, steroid-primed rats were injected (i.p.) with either PBS-BSA (control) or 5 μg of IL-1β, alone or in combination with i.c.v. administration of GABA-A and GABA-B receptor antagonists, Bicuculline and CGP 35348 (CGP) respectively. Animals were subjected to push-pull perfusion of the MPA and perfusates collected at 30 min intervals were analyzed for both NE and GABA levels using HPLC-EC. Simultaneously, serial plasma samples were obtained through jugular catheters and were analyzed for LH levels using RIA. Compared to control rats, NE levels decreased significantly in the MPA in IL-1β-treated rats (p<0.05). Concurrently, there was a significant increase in GABA levels in the MPA (p<0.05). The GABA-A receptor antagonist, bicuculline, was able to reverse the effect of IL-1β on NE and LH, while the GABA-B receptor antagonist, CGP 35348 was without any effect. This leads us to conclude that the IL-1β-induced suppression of the LH surge is most probably mediated through an increase in GABA levels in the MPA which causes a reduction in NE levels. This is probably one of the mechanisms by which IL-1β inhibits reproductive functions. PMID:19014915

  16. The involvement of luteinizing hormone (LH) and Pregnancy-Associated Glycoprotein family (PAG) in pregnancy maintenance in the pig.

    PubMed

    Panasiewicz, Grzegorz; Majewska, Marta; Szafrańska, Bozena

    2004-07-01

    The paper presents the effect of in vivo immuno-neutralization of porcine luteinizing hormone (pLH) by species-homologous porcine antiserum (anti-pLH) administrations on pregnancy maintenance and immunodetection of the PAG proteins in precipitated plasma proteins of pregnant gilts. Pregnant gilts were passively immunized with 100 ml of porcine anti-pLH (titer 1:10 000) by multiple intravenous infusions performed from 37(th) to 42(nd) day post coitum (dpc; 12-h intervals). Blood samples of pregnant gilts were taken 12 times daily from 35 until 50 dpc. Concentrations of progesterone (P(4)) and pLH were determined by radioimmunoassays in systemic blood plasma of treated gilts and control pregnant gilts. The immuno-neutralization of peripheral pLH with the use of homologous anti-pLH serum resulted in a significant reduction (p<0.001) of plasma P(4) concentrations in two out of six treated gilts only, but abortion did not occur. In the remaining four passively immunized pregnant gilts, plasma P(4) concentration was increased (p<0.001) and the abortion occurred (47 dpc) only in one of the gilts. In addition, various anti-pPAG sera were purified by sequential adsorptions with endometrial proteins of cyclic gilts. Western blotting demonstrated the expression of the PAG proteins in precipitated plasma proteins of pregnant gilts. In conclusion, the passive immuno-neutralization of porcine LH by species-homologous antiserum (anti-pLH) did not affect the pregnancy maintenance. Thus, the maintenance of mid-pregnancy in gilts may depend also on other than LH luteotrophic factors. In addition, Western analysis of precipitated plasma proteins of pregnant pigs suggests a role of the PAG family during pregnancy in the pig.

  17. The response of luteinizing hormone secretion to photoperiod is modified by the level of nutrition in female Mediterranean goats.

    PubMed

    Zarazaga, L A; Celi, I; Guzmán, J L; Malpaux, B

    2011-06-01

    This paper reports the influence of nutrition on the photoperiodic control of luteinizing hormone (LH) secretion in female Mediterranean goats (i.e., goats from the Mediterranean area in general). Ovariectomized, oestradiol-treated goats were subjected to two consecutive intervals of 3 months of long days followed by 3 months of short days (group LDSD, N=20), or vice versa (group SDLD, N=20). The LDSD and SDLD does were also randomly assigned to one of two nutrition groups that received either 1.1 (H group, N=10) or 0.7 (L group, N=10) times their maintenance requirements. Live weight and body condition score were determined weekly and LH concentrations twice per week. To establish the pulsatility of secretion of LH, three periods of intensive sampling were undertaken. Melatonin was determined after a period of 45 short or long days. All photoperiod/nutrition groups showed large variations in LH concentrations according to photoperiod, with nutrition having a significant effect (P<0.001). The mean time between the shift from long to short days and the stimulation of LH secretion, and between the shift from short to long days and the inhibition of LH secretion, was different in each nutrition group (at least P<0.05). No differences were seen in the frequency of LH pulses between the nutrition groups, but differences between sampling periods were observed (P<0.001). Melatonin secretion was not affected by food supply. These results confirm: (1) that Mediterranean female goats are sensitive to photoperiod, (2) that this environmental cue may control the timing of pituitary activity under natural conditions, and (3) suggest that nutrition plays an important role in the effect of photoperiod on LH secretion. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    PubMed

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

    1979-05-01

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

  19. Characterization of a monoclonal antibody which detects luteinizing hormone from diverse mammalian species.

    PubMed

    Matteri, R L; Roser, J F; Baldwin, D M; Lipovetsky, V; Papkoff, H

    1987-07-01

    The present study describes the development and characterization of a monoclonal antibody (518B7) generated against bovine LH (bLH). Although 518B7 was extremely specific for LH, very low species specificity was observed. A RIA using this antibody and radioiodinated equine LH (eLH) showed good sensitivity for all mammalian LH preparations tested, with the exception of human LH (15%, relative to the eLH reference standard). Activities of most mammalian LH's ranged between approximately 50-200%. Much less activity was detected with reptilian LH (less than 1.5%). Amphibian and avian LH fractions were essentially inactive. The reactivities of LH alpha and beta subunits from a variety of mammals clearly showed that the antibody reacts with the beta subunit. Sensitive RIAs were also developed utilizing 125I-bovine and 125I-rat LH. Interestingly, all hormone preparations which showed sufficient reactivity for statistical analysis within the dose ranges used in the present study (0.01-1000 ng/tube) produced a displacement curve parallel to the reference standard. We have also validated the use of 518B7 in detecting LH in serum. Parallel dilution curves relative to purified LH reference standards were observed with equine and bovine serum samples and equine pituitary extract. High (average 94%) recoveries were also seen with bovine serum with known amounts of exogenously added bLH. Similar patterns of LH secretion were detected with a RIA based upon 125I-bLH and 518B7 and a previously described polyclonal antibody-based RIA in bovine serum samples during estrus. Thus, a monoclonal antibody for LH has been produced which can be used to develop sensitive and specific RIAs in many different mammalian species.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Early spring sex differences in luteinizing hormone response to gonadotropin releasing hormone in co-occurring resident and migrant dark-eyed juncos (Junco hyemalis).

    PubMed

    Greives, Timothy J; Fudickar, Adam M; Atwell, Jonathan W; Meddle, Simone L; Ketterson, Ellen D

    2016-09-15

    To optimally time reproduction, animals must coordinate changes in the hypothalamo-pituitary-gonadal (HPG) axis. The extent of intra-species variation in seasonal timing of reproductive function is considerable, both within and among populations. Dark-eyed junco (Junco hyemalis) populations are known to differ in their reproductive timing response to cues experienced in the same habitat in late winter/early spring. Specifically in juncos cohabitating on shared wintering grounds, residents initiate breeding and reproductive activity but migrants delay reproductive development and prepare to migrate before breeding. Here, we test the hypothesis that the pituitary gland acts as a 'control point' to modulate differential HPG axis activity across populations. We sampled free-living resident and migrant juncos on their shared over-wintering grounds in March, thus all individuals were experiencing the same environmental cues, including photoperiod. We predicted that during this critical time of transition, residents would more readily respond to repeated gonadotropin releasing hormone (GnRH) stimulation with increases in luteinizing hormone (LH), in contrast to migrants, which should delay full reproductive activity. Our data indicate that migrant females, while still on the overwintering grounds, have a reduced LH response to repeated GnRH injections compared to resident females. Male migrant and resident birds did not differ in their responsiveness to repeated GnRH. Our results suggest a sex difference in the costs of mistimed activation of the HPG axis, with female migrants being less responsive than residents females and males to repeated stimulation. Further, our data implicate a key role for the pituitary in regulating appropriate reproductive timing responses.

  1. Follicle suppression of circulating follicle-stimulating hormone and luteinizing hormone before versus after emergence of the ovulatory wave in mares.

    PubMed

    Ginther, O J; Gastal, E L; Gastal, M O; Duarte, L F; Beg, M A

    2009-09-01

    The effect of the ovarian follicles on plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) before versus after the expected emergence of the ovulatory follicular wave was studied on Days 0 to 18 (Day 0=ovulation) in four groups of mares (n=6/group). In addition to a control group, all follicles >/=6mm in diameter were ablated on Days 0.5, 6.5, or 12.5 in a herd of mares with reported emergence at 6mm of the future ovulatory follicle on mean Day 10.5. Concentrations of FSH were not different between the Day-0.5 or Day-6.5 ablation groups and the corresponding controls. However, ablation on Day 12.5 resulted in an immediate FSH increase (group-by-day interaction, P<0.003). For LH, ablation on Day 0.5 resulted in an interaction (P<0.02), partially from lower (P<0.05) concentrations on each of Days 15.5 to 18.0 than that in the controls, whereas ablation on Days 6.5 or 12.5 did not result in a significant group effect or interaction. Testosterone concentration, but not progesterone or estradiol concentration, was lower (P<0.04) on Day 2 in the Day-0.5 ablation group than that in the controls. We inferred that follicles did not contain adequate FSH suppressors on Days 0.5 and 6.5 and that they were present only in the Day-12.5 ablation group or after the expected emergence of the ovulatory wave. The hypothesis of an association between low postovulatory concentrations of an ovarian steroid and low concentrations of LH after Day 15 was supported.

  2. Modulation of in vitro DNA synthesis in the chicken ovarian granulosa cell follicular hierarchy by follicle-stimulating hormone and luteinizing hormone.

    PubMed

    McElroy, A P; Caldwell, D J; Proudman, J A; Hargis, B M

    2004-03-01

    Folliculogenesis in domestic hens appears to be controlled by numerous factors, particularly the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The involvement of LH in follicular steroidogenesis has been described in some detail; however, the specific role of FSH has remained elusive. In 3 experiments, the effects of ovine (o)- or chicken (c)-derived FSH (oFSH, cFSH) or LH (oLH, cLH) were evaluated on in vitro DNA synthesis [3H-thymidine (3H-TdR) incorporation], indicative of cellular proliferation, of granulosa cells from F1, F3, or F5-6 preovulatory follicles. In experiment 1, oFSH or cFSH stimulated (P < 0.05) and oLH or cLH decreased DNA synthesis by F1 granulosa cells. In experiment 2, oFSH resulted in concentration-related changes in DNA synthesis by F5-6 granulosa cells; however, no significant changes were observed in F1 or F3 granulosa cells. No effect of oLH was observed on granulosa cell proliferation from any of the follicles. Similar to oFSH, cFSH resulted in concentration-related increases in DNA synthesis in granulosa cells from F5-6 follicles with smaller magnitude changes in proliferation of F1 or F3 granulosa cells. Granulosa cells from F5-6 or F3 follicles had small increases in DNA synthesis in response to cLH. These data support the proposed role for FSH in granulosa cell proliferation, possibly contributing to follicle growth, and suggest that in vitro 3H-TdR incorporation by granulosa cells may provide a sensitive and selective bioassay for chicken gonadotropin preparations. Furthermore, data suggest that proliferative responsiveness of granulosa cells to FSH or LH may differ depending on position of follicles in the preovulatory hierarchy.

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

    PubMed

    Rudolf, Faidiban O; Kadokawa, Hiroya

    2016-01-01

    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.

  4. Effects of intravenous administration of neurokinin receptor subtype-selective agonists on gonadotropin-releasing hormone pulse generator activity and luteinizing hormone secretion in goats

    PubMed Central

    YAMAMURA, Takashi; WAKABAYASHI, Yoshihiro; OHKURA, Satoshi; NAVARRO, Victor M.; OKAMURA, Hiroaki

    2014-01-01

    Recent evidence suggests that neurokinin B (NKB), a member of the neurokinin (tachykinin) peptide family, plays a pivotal role in gonadotropin-releasing hormone (GnRH) pulse generation. Three types of neurokinin receptors (NKRs), NK1R, NK2R and NK3R, are found in the brain. Although NKB preferentially binds to NK3R, other NKRs are possibly also involved in NKB action. The present study examined the effects of intravenous administration of the NKR subtype-selective agonists GR73632 (NK1R), GR64349 (NK2R), and senktide (NK3R) on GnRH pulse generator activity and luteinizing hormone (LH) secretion. Multiple-unit activity (MUA) was monitored in ovariectomized goats (n = 5) implanted with recording electrodes. Characteristic increases in MUA (MUA volleys) were considered GnRH pulse generator activity. Although three NKR agonists dose-dependently induced an MUA volley and an accompanying increase in LH secretion, the efficacy in inducing the volley markedly differed. As little as 10 nmol of senktide induced an MUA volley in all goats, whereas a dose of 1000 nmol was only effective for the NK1R and NK2R agonists in two and four goats, respectively. When the treatment failed to evoke an MUA volley, no apparent change was observed in the MUA or LH secretion. Similar effects of the NK2R and NK3R agonists were observed in the presence of estradiol. The results demonstrated that NK3R plays a predominant role in GnRH pulse generation and suggested that the contributions of NK1R and NK2R to this mechanism may be few, if any, in goats. PMID:25345909

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

    PubMed

    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

    2012-06-01

    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 < 0.01), and ASR (P < 0.05). With regards to genotype and its interaction with age, only the SNP of G51656T in LHR gene had significant effect on SD (P < 0.05, P < 0.01; respectively). The association result showed that bulls with AG genotype had higher FSM than bulls with AA and GG genotype in LHR at 51,703 locus (P < 0.10), and 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.

  6. Restraint-induced changes in serum luteinizing hormone, prolactin, growth hormone and corticosterone levels in rats: effect of superior cervical ganglionectomy.

    PubMed

    Martín, A I; López-Calderón, A; Tresguerres, J A; González-Quijano, M I; Cardinali, D P

    1995-02-01

    From about 10 to 36 h after superior cervical ganglionectomy (SCGx), peripheral sympathetic nerve terminals in the median eminence degenerate, nerve ending content is released, and a transient period of increased postsynaptic activity ensues. After this time, an irreversible, paralytic phase is established in the denervated territory. The present experiment was undertaken to examine, at single points during the wallerian degeneration phase (24 h after SCGx) and during the paralytic phase (10 days after denervation), the participation of peripheral sympathetic nerves in restraint-stress-induced changes of circulating luteinizing hormone (LH), prolactin (PRL), growth hormone (GH) and corticosterone levels. During the wallerian degeneration phase, serum LH did not augment after stress, as it did in sham-operated controls. In the paralytic phase, the poststress increases in LH attained similar values in sham-operated and SCGx rats. Immobilization stress augmented PRL levels to a similar extent in sham-operated and SCGx rats either 24 h or 10 days after surgery. During the wallerian degeneration phase, a decrease in serum GH levels was found in unrestrained rats. Immobilization stress decreased GH levels to 5-12% of unrestrained values in sham-operated and SCGx rats at both examination time points after surgery. Rats studied 24 h after SCGx exhibited significantly augmented serum corticosterone levels and failed to show restraint-stress-induced stimulation of corticosterone release. In rats subjected to SCGx 10 days earlier, both basal and poststress levels of corticosterone did not differ from sham-operated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Effects of alcohol on pulsatile luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion in the adult male rat

    SciTech Connect

    Badger, T.M.; Abdallah, M.M.; Hayden, J.B. )

    1989-02-09

    To determine possible hypothalamic actions of alcohol on hormone secretion, the effects of acute intragastric alcohol on plasma LH and FSH pulsations were studied. One jugular and one intragastric cannula were surgically implanted into adult male Sprague Dawley rats. Eight days later, rats were bilaterally castrated at 1400 h and infused intragastrically with either saline or 3 g/kg ethanol between 0700 h 0800 h the next days. Blood samples (300 microliters) were collected every 5 min for 3 h (starting at 0800 h), centrifuged and the plasma was frozen for LH and FSH radioimmunoassay. The blood cells were resuspended in saline and returned to the animal immediately following the next sample collection. While the mean plasma LH or FSH concentration did not vary significantly between the alcohol-treated and saline-treated rats, the mean LH (but not FSH) pulse frequency was lower in ethanol-treated rats (3.3 {plus minus} 0.25 pulses/3 h) than saline-treated controls (7.2 {plus minus} 0.3 pulses/3 h). In addition, mean area under the OH pulses were significantly greater in ethanol-treated than saline controls. These data suggest that: (1) ethanol acts to reduce the frequency of LHRH release for the hypothalamus and increase the area under each LH pulse; and (2) LH and FSH secretion are differentially regulated.

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

    SciTech Connect

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

    1987-02-01

    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.

  9. Receptors for luteinizing hormone-releasing hormone (GnRH) as therapeutic targets in triple negative breast cancers (TNBC).

    PubMed

    Kwok, C W; Treeck, O; Buchholz, S; Seitz, S; Ortmann, O; Engel, J B

    2015-09-01

    Triple negative breast cancers express receptors for gonadotropin-releasing hormone (GnRH) in more than 50% of the cases, which can be targeted with peptidic analogs of GnRH, such as triptorelin. The current study investigates cytotoxic activity of triptorelin as a monotherapy and in treatment combinations with chemotherapeutic agents and inhibitors of the PI3K and the ERK pathways in in vitro models of triple negative breast cancers (TNBC). GnRH receptor expression of TNBC cell lines MDA-MB-231 and HCC1806 was investigated. Cells were treated with triptorelin, chemotherapeutic agents (cisplatin, docetaxel, AEZS-112), PI3K/AKT inhibitors (perifosine, AEZS-129), an ERK inhibitor (AEZS-134), and dual PI3K/ERK inhibitor AEZS-136 applied as single agent therapies and in combinations. MDA-MB-231 and HCC1806 TNBC cells both expressed receptors for GnRH on messenger (m)RNA and protein level and were found sensitive to triptorelin with a respective median effective concentration (EC50) of 31.21 ± 0.21 and 58.50 ± 19.50. Synergistic effects occurred when triptorelin was combined with cisplatin. In HCC1806 cells, synergy occurred when triptorelin was applied with PI3K/AKT inhibitors perifosine and AEZS-129. In MDA-MB-231 cells, synergy was observed after co-treatment with triptorelin and ERK inhibitor AEZS-134 and dual PI3K/ERK inhibitor AEZS-136. GnRH receptors on TNBC cells can be used for targeted therapy of these cancers with GnRH agonist triptorelin. Treatment combinations based on triptorelin and PI3K and ERK inhibitors and chemotherapeutic agent cisplatin have synergistic effects in in vitro models of TNBC. If confirmed in vivo, clinical trials based on triptorelin and cisplatin could be quickly carried out, as triptorelin is FDA approved for other indications and known to be well tolerated.

  10. Influence of age on pulsatile luteinizing hormone release and responsiveness of the gonadotrophs to sex hormone feedback in men.

    PubMed

    Deslypere, J P; Kaufman, J M; Vermeulen, T; Vogelaers, D; Vandalem, J L; Vermeulen, A

    1987-01-01

    The influence of aging on serum LH and testosterone (T) pulse frequency and gonadotroph sensitivity to androgen and estrogen feedback was studied in young (less than 55 yr old) and elderly (greater than 65 yr) Trappist monks. LH pulse frequency (sampling interval, 20 min) was significantly lower [0.25 +/- 0.03 (+/- SEM) vs. 0.38 +/- 0.02 pulses/h; P less than 0.01] in elderly (n = 21) than in young monks (n = 27); the pulse amplitudes were similar. Similarly, T pulse frequency was lower in the elderly than in the young monks (0.13 +/- 0.04 vs. 0.23 +/- 0.02 pulses/h; P less than 0.01). In elderly men, the hypothalamo-pituitary complex was more sensitive to 5 alpha-androstan-17 beta-ol-3-one feedback, as determined by the decrease in serum LH and T levels. Moreover, during 5 alpha-androstan-17 beta-ol-3-one (125 mg/day, percutaneously, for 10 days) administration, the LH response to LHRH (100 micrograms, iv) was significantly higher in the elderly men compared to the pretreatment response. During estradiol (1.5 mg/day, percutaneously for 10 days) administration, the LH response to LHRH was decreased in the elderly men, but unchanged in the young men, suggesting greater responsiveness to estradiol in the elderly men. We conclude that in aged men, decreased testicular androgen secretion is not exclusively the consequence of a primary testicular alteration, but that important changes occur in hypothalamo-pituitary function, specifically decreased LH pulse frequency and increased LH responsiveness to sex hormone feedback.

  11. Recombinant-human luteinizing hormone (r-hLH) as ovulatory stimulus in superovulated does.

    PubMed

    Peinado, J A; Molina, I; Pla, M; Tresguerres, J A; Romeu, A

    1995-01-01

    To study the effects of r-hLH as ovulatory stimulus in does. New Zealand does, 18 wk old, in estrus, received 25 IU of pregnant mare serum gonadotropin (PMSG) followed at 48 h either by 50 IU of r-hLH (n = 20) or hCG (n = 20) to induce follicular growth and ovulation. All does were previously artificially inseminated to avoid endogenous LH surge. Half of the animals receiving r-hLH (n = 10) or hCG (n = 10) were killed at 72 h after the hormone administration, and the remaining half were killed at 14 days. At 72 h the number of corpora lutea and preovulatory follicles was determined, and fertilization rate, embryo quality, degree of embryonic development, and oviductal transit were all assessed. On day 14 the number corpora lutea and implanted embryos were counted, and implantation rate was determined. Median and interquartile ranges were calculated for each parameter. At 72 h the median for corpora lutea was 8 (7-10) in the r-hLH group vs 13 (10-14) in the hCG group (P = 0.009); preopvulatory follicles were 7 (6-10) vs 0 (0-0) (P = 0.0007); the percentage of good-quality embryos was 71.4% (54.5-75) vs 33.3% (25-37.5) (P = 0.001), for intermediate-quality embryos it was 25% (14.3-36.4) vs 33.3% (25-38.5), and the percentage of degenerated embryos was 0% (0-12.5) vs 33.3% (25-37.5) (P = 0.015), respectively. Fertilization rates were similar in both groups. Embryonic development was more homogeneous in the animals receiving r-hLH (8 to > or = 16 cells) compared to those receiving hCG (2 to > or = 16 cells). The median of embryos still in oviducts at 72 h was significantly higher in the hCG group [6 (4-13)] than in the r-hLH group [0 (0-4)] (P = 0.41). At 14 days the median of corpora lutea was higher in the hCG [12 (11-16)] than in the r-hLH group [10 (7-13)] (P = 0.008), but no differences were noted in the number of implanted embryos. Implantation rate was higher in the r-hLH group [100 (92.3-100)] than in the hCG group [87.5 (83.3-94.1)] (P = 0.056). At the studied

  12. Reference Ranges and Association of Age and Lifestyle Characteristics with Testosterone, Sex Hormone Binding Globulin, and Luteinizing Hormone among 1166 Western Chinese Men

    PubMed Central

    Shen, Xubo; Wang, Ruifeng; Yu, Na; Shi, Yongjun; Li, Honggang; Xiong, Chengliang; Li, Yan; Zhou, Yuanzhong

    2016-01-01

    Decreased total testosterone (TT) is the recommended metric to identify age-related hypogonadism. However, average TT and the extent to which it varies by age, can vary substantially among different populations. Population-specific reference ranges are needed to understand normal versus abnormal TT levels. Therefore, the goal for this study was to describe androgen concentrations and their correlates among Western Chinese men. We completed a population-based, cross-sectional study including 227 young adults (YA) (20–39 years) and 939 older adults (OA) (40–89 years). We measured TT, sex-hormone binding globulin (SHBG), luteinizing hormone (LH), testosterone secreting index (TSI), and calculated free testosterone (cFT). Reference ranges for this population were determined using average YA concentrations. Multivariable regression models were used to predict hormone concentrations adjusting for age, waist-to-height ratio (WHR), marital status, education, occupation, smoking, alcohol, blood glucose, and blood pressure. Among OA, 3.8% had low TT, 15.2% had low cFT, 26.3% had low TSI, 21.6% had high SHBG, and 6.1% had high LH. Average cFT was significantly lower in OA (0.30 nmol/L; standard deviation (SD): 0.09) versus YA (0.37; SD: 0.11) but TT was not different in OA (16.82 nmol/L; SD: 4.80) versus YA (16.88; SD: 5.29). In adjusted models increasing age was significantly associated with increased SHBG or LH, and decreased cFT or TSI; however, TT was not significantly associated with age (β = 0.02 nmol/L; 95% confidence interval (CI): -0.01, 0.04). Higher WHR was associated with significantly decreased TT, SHBG, TSI, and LH. The only variable significantly related to cFT was age (β = -0.0033; 95% CI:-0.0037, -0.0028); suggesting that cFT measurements would not be confounded by other lifestyle factors. In conclusion, cFT, but not TT, varies with age in this population, suggesting cFT may be a better potential marker for age-related androgen deficiency than TT among

  13. Comparison of mechanisms of action of luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix and LHRH agonist triptorelin on the gene expression of pituitary LHRH receptors in rats

    PubMed Central

    Kovacs, Magdolna; Schally, Andrew V.

    2001-01-01

    The mechanisms through which luteinizing hormone (LH)-releasing hormone (LHRH) antagonists suppress pituitary gonadotroph functions and LHRH-receptor (LHRH-R) expression are incompletely understood. Consequently, we investigated the direct effect of LHRH antagonist cetrorelix in vitro on the expression of the pituitary LHRH-R gene and its ability to counteract the exogenous LHRH and the agonist triptorelin in the regulation of this gene. We also compared the effects of chronic administration of cetrorelix and triptorelin on the LHRH-R mRNA level and gonadotropin secretion in ovariectomized (OVX) and normal female rats. The exposure of pituitary cells in vitro to 3-min pulses of 1 nM LHRH or 0.1 nM triptorelin for 5 h increased the LHRH-R mRNA level by 77–88%. Continuous perfusion of the cells with 50 nM cetrorelix did not cause any significant changes, but prevented the stimulatory effect of LHRH pulses on the receptor mRNA expression. In OVX rats, 10 days after administration of a depot formulation of cetrorelix, releasing 100 μg of peptide daily, the elevated LHRH-R mRNA level was decreased by 73%, whereas daily injection of 100 μg of triptorelin caused a 41% suppression. In normal female rats, cetrorelix treatment suppressed the LHRH-R mRNA level by 33%, but triptorelin increased it by 150%. The highly elevated serum LH levels in OVX rats and the normal LH concentration of cycling rats were rapidly and completely suppressed by cetrorelix. Triptorelin decreased the serum LH in OVX rats to the precastration level, but had no effect on basal LH in normal rats. Our results confirm that LHRH antagonists, such as cetrorelix, inhibit the gene expression of pituitary LHRH-R indirectly, by counteracting the stimulatory effect of LHRH. A rapid suppression of serum LH by LHRH antagonists would be advantageous in the treatment of sex hormone-dependent tumors and other conditions. PMID:11593037

  14. Development of a porcine follicle-stimulating hormone and porcine luteinizing hormone induced ovulation protocol in the seasonally anoestrus brushtail possum (Trichosurus vulpecula).

    PubMed

    Glazier, A M; Molinia, F C

    2002-01-01

    Monovulatory brushtail possums (Trichosurus vulpecula) were stimulated with exogenous hormones during seasonal anoestrus to overcome ovarian insensitivity and induce ovulation. Seasonal ovarian insensitivity to pregnant mare serum gonadotrophin (PMSG) was overcome by a new porcine follicle-stimulating hormone/porcine luteinizing hormone (pFSH/pLH) protocol. This protocol was refined because the original treatment produced oocytes with abnormal morphology. Possums (n = 12 per group) received eight injections of pFSH of 1.5, 3.0 or 6.0 mg per injection (at 12-h intervals for 4 consecutive days). Ovulation was induced 12 h after the final pFSH injection with a 4-mg injection of pLH. Control animals were treated with the established protocol of a single injection of 15 IU of PMSG, followed 48 h later with an injection of 4 mg of pLH. All females responded to pFSH/pLH treatment, although optimal stimulation occurred in those receiving 8 x 3 mg pFSH, with 13-14 ovulations and recovery of 11-12 oocytes per female (8 x 1.5 mg pFSH: 13 ovulations, 8-9 oocytes; 8 x 6 mg pFSH: 7-8 ovulations, 4-5 oocytes). In contrast, only seven of 12 females responded to PMSG/pLH and, of those responding, only 2-3 ovulations occurred and only 1-2 oocytes per female were recovered. However, around 80% of oocytes recovered after PMSG/pLH treatment had undergone nuclear maturation (metaphase II/1st polar body) compared with around 60% of oocytes from pFSH/pLH-treated animals. In possums killed from 27 to 39 h after pLH treatment, ovulation onset was first observed from 30 h and by 31.5 h, all animals had completed ovulation. Laparoscopic artificial insemination (LAI) was performed on pFSH/pLH-treated animals to determine whether the oocytes produced were capable of fertilization. Uterine LAI performed 27.5-28.5 h after pLH treatment yielded 11/26 fertilized oocytes (up to 4-cell stage), whereas vaginal LAI performed 13-14 h after pLH treatment yielded 21/53 fertilized oocytes. A proportion of

  15. Combination of long-acting microcapsules of the D-tryptophan-6 analog of luteinizing hormone-releasing hormone with chemotherapy: investigation in the rat prostate cancer model.

    PubMed Central

    Schally, A V; Redding, T W

    1985-01-01

    The effect of combining hormonal treatment consisting of long-acting microcapsules of the agonist [D-Trp6]LH-RH (the D-tryptophan-6 analog of luteinizing hormone-releasing hormone) with the chemotherapeutic agent cyclophosphamide was investigated in the Dunning R-3327H rat prostate cancer model. Microcapsules of [D-Trp6]LH-RH formulated from poly(DL-lactide-co-glycolide) and calculated to release a controlled dose of 25 micrograms/day were injected intramuscularly once a month. Cyclophosphamide (Cytoxan) (5 mg/kg of body weight) was injected intraperitoneally twice a week. When the therapy was started 90 days after tumor transplantation--at the time that the cancers were well developed-and was continued for 2 months, tumor volume was significantly reduced by the microcapsules or Cytoxan given alone. The combination of these two agents similarly inhibited tumor growth but did not show a synergistic effect. In another study, the treatment was started 2 months after transplantation, when the developing tumors measured 60-70 mm3. Throughout the treatment period of 100 days, the microcapsules of [D-Trp6]LH-RH reduced tumor volume more than Cytoxan did, and the combination of the two drugs appeared to completely arrest tumor growth. Tumor weights also were diminished significantly in all experimental groups, the decrease in weight being smaller in the Cytoxan-treated group than in rats that received the microcapsules. The combination of Cytoxan plus the microcapsules was 10-100 times more effective than the single agents in reducing tumor weights. In both experiments, testes and ventral prostate weights were significantly diminished, serum testosterone was suppressed to undetectable levels, and prolactin values were reduced by administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Cytoxan. These results in rats suggest that combined administration of long acting microcapsules of [D-Trp6]LH-RH with a chemotherapeutic agent, started soon after the

  16. LIGHT AND ELECTRON MICROSCOPE LOCALIZATION OF BINDING SITES OF ANTIBODIES AGAINST OVINE LUTEINIZING HORMONE AND ITS TWO SUBUNITS IN RAT ADENOHYPOPHYSIS USING PEROXIDASE-LABELED ANTIBODY TECHNIQUE

    PubMed Central

    Tougard, C.; Kerdelhue, B.; Tixier-Vidal, A.; Jutisz, M.

    1973-01-01

    The binding sites of antisera generated in the guinea pig against ovine luteinizing hormone (oLH) and its two subunits (oLHα and oLHβ) have been localized in rat anterior pituitaries taken from normal or castrated males and from ovariectomized females with the peroxidase-labeled antibody method, using light and electron microscopy. With the light microscope, the cells positive with antiserum to ovine luteinizing hormone (A-oLH) were violet after the Alcian blue-periodic acid-Schiff (AB-PAS) staining; they were also positive for A-oLHα and for A-oLHβ and, from castrated males, they displayed an increased affinity for A-oLHβ. Another cell type which was blue after the AB-PAS method reacted with the A-oLHα only; these cells, presumably thyrotropic cells, were retracted after castration and, besides their affinity for A-oLHα, acquired an affinity for A-oLHβ. As seen through the electron microscope, two cell types were positive for A-oLH, A-oLHβ, and A-oLHα and may be identified as luteinizing hormone-secreting cells. Type A cells were characterized by two classes of rounded, secretory granules. Type B cells were smaller and contained only small secretory granules. 1 mo after the rats were castrated the type A cells were hypertrophied and vacuolized. In both cases the secretory granules were the main sites of the antigenicity with the three antisera. A positive reaction was also found in the cytoplasm, particularly in hypertrophied cells from ovariectomized females and with A-oLHβ. The cisternae of the rough endoplasmic reticulum were usually negative, except in highly degranulated cells from ovariectomized females and with A-oLHβ. PMID:4583879

  17. Synchronization of ovulation in cyclic gilts with porcine luteinizing hormone (pLH) and its effects on reproductive function.

    PubMed

    Degenstein, K L; O'Donoghue, R; Patterson, J L; Beltranena, E; Ambrose, D J; Foxcroft, G R; Dyck, M K

    2008-10-15

    The overall objective was to evaluate the use of porcine luteinizing hormone (pLH) for synchronization of ovulation in cyclic gilts and its effect on reproductive function. In an initial study, four littermate pairs of cyclic gilts were given altrenogest (15 mg/d for 14 d). Gilts received 500 microg cloprostenol (Day 15), 600 IU equine chorionic gonadotropin (eCG) (Day 16) and either 5mg pLH or saline (Control) 80 h after eCG. Blood samples were collected every 4h, from 8h before pLH/saline treatment to the end of estrus. Following estrus detection, transcutaneous real-time ultrasonography and AI, all gilts were slaughtered 6d after the estimated time of ovulation. Peak plasma pLH concentrations (during the LH surge), as well as the amplitude of the LH surge, were greater in pLH-treated gilts than in the control (P=0.01). However, there were no significant differences between treatments in the timing and duration of estrus, or the timing of ovulation within the estrous period. In a second study, 45 cyclic gilts received altrenogest for 14-18d, 600 IU eCG (24h after last altrenogest), and 5mg pLH, 750 IU human chorionic gonadotropin (hCG), or saline, 80 h after eCG. For gilts given pLH or hCG, the diameter of the largest follicle before the onset of ovulation (mean+/-S.E.M.; 8.1+/-0.2 and 8.1+/-0.2mm, respectively) was smaller than in control gilts (8.6+/-0.2mm, P=0.05). The pLH and hCG groups ovulated sooner after treatment compared to the saline-treated group (43.2+/-2.5, 47.6+/-2.5 and 59.5+/-2.5h, respectively; P<0.01), with the most synchronous ovulation (P<0.01) in pLH-treated gilts. Embryo quality (total cell counts and embryo diameter) was not significantly different among groups. In conclusion, pLH reliably synchronized ovulation in cyclic gilts without significantly affecting embryo quality.

  18. [The efficacy and safety of domestic luteinizing hormone-releasing hormone analogue and low-dose norethindrone "add-back" therapy in the treatment of endometriosis].

    PubMed

    Zhang, S; Ye, G; Chen, H

    2000-08-01

    To study the efficacy and safety of combining domestic luteinizing hormone-releasing hormone analogue(LHRH-a) with low-dose norethindrone in the treatment of endometriosis. Seventy-seven women with endometriosis were randomized into one of the following two groups. Group A (n = 36) were treated with LHRH-a (150 micrograms/d, i.m.) plus norethindrone (2.5 mg/d, p.o.) and group B (n = 41) received only LHRH-a (150 micrograms/d, i.m.) for 3 to 6 months. Symptoms and signs were recorded before and after the treatment. Liver and renal functions, lipid and bone metabolism and speed of sound (SOS) in the tibia were also examined at the same time. All data were analyzed using paired and grouped Student's t-tests. Total subjective symptom scores of group A showed 82% decrease at 3 months and 94% at 6 months of treatment (P < 0.01). Reductions in endometriotic foci were 34% and 61% at 3 and 6 months, respectively (P < 0.01). Of group B, there were 77% and 90% decreases in total subjective symptom scores at 3 and 6 months of treatment (P < 0.01). Reductions of 37% and 38% in endometriotic foci were observed at 3 and 6 months, respectively (P < 0.01). Liver and renal functions and fast blood sugar of both groups were all in normal range. Triglyceride (TG), apolipoproteinA (ApoA), serum calcium, phosphorus and alkaline phosphatase levels of group B increased significantly after treatment. And significant differences between the two groups were observed. There's no change of SOS in the tibia within or between the two groups before and after treatment. The percentages of hemorrhage in the group A and B were 18% and 38%, respectively. The percentages of hot flush and the other vasomotor symptoms were 14% and 41%, respectively (P < 0.01). Domestic LHRH-a combined with low-dose norethindrone was effective in the treatment of endometriosis. It could also improve the symptom of hypoestrogenemia, decrease hemorrhage rete and bone turn-over.

  19. Copper amplification of prostaglandin E/sub 2/ stimulation of the release of luteinizing hormone-releasing hormone is a postreceptor event

    SciTech Connect

    Barnea, A.; Cho, G.

    1987-01-01

    The authors have shown that copper amplifies prostaglandin E/sub 2/ (PGE/sub 2/) stimulation of luteinizing hormone-releasing hormone (LH-RH) from explants of the median eminence area (MEA) and that this process is calcium-dependent. Since a Ca-cAMP pathway has been implicated in PGE/sub 2/ action on the LH-RH neuron, in this study the authors wished to ascertain if copper exerts its effect on the PGE/sub 2/ receptor or on a postreceptor component involved in PGE/sub 2/ action. MEA of adult male rats were incubated for 5 min with 200 ..mu..M Cu/histidine and then incubated for 15 min either with 10 ..mu..M PGE/sub 2/ (Cu/PGE/sub 2/), 100 ..mu..M forskolin (Cu/forskolin), or 1 mM 8-bromoadenosine 3',5'-cyclic monophosphate (Cu/cAMP). Basal release of LH-RH was 4.6 +/- 0.45 pg/15 min per MEA determined by radioimmunoassay. Net stimulated release during the 15-min exposure to PGE/sub 2/, forskolin, or 8-bromoadenosine 3',5'-cyclic monophosphate was 3.6 +/- 0.52, 3.1 +/- 0.39, and 1.6 +/- 0.42 pg/15 min per MEA, respectively. Net stimulated release after exposure to Cu/PGE/sub 2/, Cu/forskolin, or Cu/cAMP indicated that copper amplifies the action of PGE/sub 2/ and forskolin but not cAMP action. When MEA were exposed to a mixture of PGE/sub 2/ and forskolin for 15 min, the effects of these two secretagogues on LH-RH release were not additive. In contrast to PGE/sub 2/ and forskolin, copper did not amplify K/sup +/ stimulation of OH-RH release. These results are supportive of the proposition that PGE/sub 2/ stimulation of OH-RH release is mediated by the Ca-cAMP pathway and that copper amplification of PGE/sub 2/ action is a postreceptor event.

  20. Lead (Pb) alters the norepinephrine-induced secretion of luteinizing hormone releasing hormone from the median eminence of adult male rats in vitro

    SciTech Connect

    Bratton, G.R.; Hiney, J.K.; Dees, W.L. )

    1994-01-01

    In the present study, the authors evaluated the in vitro effects of lead (Pb) on basal and stimulated luteinizing hormone releasing hormone (LHRH) and Prostaglandin E[sub 2] (PGE[sub 2]) secretion. Median eminences (ME) were removed from brains of adult male rats and preincubated for 15 minutes in Krebs-Ringer bicarbonate glucose buffer in an atmosphere of 95% O[sub 2]-5% CO[sub 2]. These media were discarded and all MEs were subjected to one of the following experiments. In Experiment 1, all MEs were incubated for 30 minutes in medium only. These media were collected and replaced with medium only (controls) or with medium containing Pb doses ranging from 5 to 20 [mu]M. After this 60-minute incubation, media were collected, then replaced with new medium containing 60 [mu]M norepinephrine (NE), or NE plus each dose of Pb, then incubated for a final 30-minute period. Experiment 2 was conducted as above, except PGE[sub 2] (2.8 [mu]M) replaced the NE. In both experiments, the amounts of LHRH released was measured by RIA. In experiment 3, NE was again used for the challenge; however, this time, the amount of PGE[sub 2] released was measured by RIA. Results indicate that Pb did not alter basal LHRH release, but compared with controls, significantly blocked NE-induced LHRH release in a dose-related manner. Conversely, Pb had no effect on the PGE[sub 2]-induced release of LHRH. Additionally, Pb did not alter basal PGE[sub 2] release; however, it significantly blocked the NE-induced release of PGE[sub 2]. Since NE-induced LHRH release is mediated by PGE[sub 2], these results support the hypothesis that Pb is capable of altering the hypothalamus and suggest that this effect is due, at least in part, to the diminished PGE[sub 2] synthesis/release within the ME, resulting in diminished LHRH secretion.

  1. Circadian rhythm disruption by a novel running wheel: roles of exercise and arousal in blockade of the luteinizing hormone surge.

    PubMed

    Duncan, Marilyn J; Franklin, Kathleen M; Peng, Xiaoli; Yun, Christopher; Legan, Sandra J

    2014-05-28

    Exposure of proestrous Syrian hamsters to a new room, cage, and novel running wheel blocks the luteinizing hormone (LH) surge until the next day in ~75% of hamsters [1]. The studies described here tested the hypotheses that 1) exercise and/or 2) orexinergic neurotransmission mediate novel wheel blockade of the LH surge and circadian phase advances. Female hamsters were exposed to a 14L:10D photoperiod and activity rhythms were monitored with infra-red detectors. In Expt. 1, to test the effect of exercise, hamsters received jugular cannulae and on the next day, proestrus (Day 1), shortly before zeitgeber time 5 (ZT 5, 7h before lights-off) the hamsters were transported to the laboratory. After obtaining a blood sample at ZT 5, the hamsters were transferred to a new cage with a novel wheel that was either freely rotating (unlocked), or locked until ZT 9, and exposed to constant darkness (DD). Blood samples were collected hourly for 2days from ZT 5-11 under red light for determination of plasma LH levels by radioimmunoassay. Running rhythms were monitored continuously for the next 10-14days. The locked wheels were as effective as unlocked wheels in blocking LH surges (no Day 1 LH surge in 6/9 versus 8/8 hamsters, P>0.05) and phase advances in the activity rhythms did not differ between the groups (P=0.28), suggesting that intense exercise is not essential for novel wheel blockade and phase advance of the proestrous LH surge. Expt. 2 tested whether orexin neurotransmission is essential for these effects. Hamsters were treated the same as those in Expt. 1 except that they were injected (i.p.) at ZT 4.5 and 5 with either the orexin 1 receptor antagonist SB334867 (15mg/kg per injection) or vehicle (25% DMSO in 2-hydroxypropyl-beta-cyclodextrin (HCD)). SB-334867 inhibited novel wheel blockade of the LH surge (surges blocked in 2/6 SB334867-injected animals versus 16/18 vehicle-injected animals, P<0.02) and also inhibited wheel running and circadian phase shifts, indicating

  2. Effect of different seasons on concentration of plasma luteinizing hormone and seminal quality vis-à-vis freezability of buffalo bulls ( Bubalus bubalis)

    NASA Astrophysics Data System (ADS)

    Bahga, C. S.; Khokar, B. S.

    1991-12-01

    Seasonal variations in semen quality, freezability and plasma luteinizing hormone (LH) levels were studied between summer and spring. Semen volume, density and initial sperm motility did not differ significantly between different seasons. Plasma LH decreased between summer and spring but the differences were, however, not significant. Pre-freezing motility did not differ significantly but post-freezing motility varied significantly ( P<0.01) between seasons. Post-freezing motility was lowest during summer and highest during winter. It can be concluded that summer spermatozoa may be fragile and cannot withstand freezing stress. To increase reproductive efficiency in buffalo during summer, semen should be frozen during winter and spring and used during hot weather conditions. Seasonal variations in plasma LH levels were insignificant.

  3. Actions of estradiol on discrete attributes of the luteinizing hormone pulse signal in man. Studies in postmenopausal women treated with pure estradiol.

    PubMed Central

    Veldhuis, J D; Evans, W S; Rogol, A D; Thorner, M O; Stumpf, P

    1987-01-01

    We assessed the time-dependent impact of estradiol on properties of the luteinizing hormone (LH) pulse signal in 12 hypoestrogenemic postmenopausal volunteers studied basally and after 1, 5, 10, and 30 d of estradiol delivery via an intravaginal Silastic ring. Computerized analysis of the plasma LH time series revealed a significant decrease in LH pulse frequency within 24 h of estrogen treatment, followed by a secondary increase (days 5 and 10), and then a sustained decline (day 30) in LH pulsatility. Estradiol also significantly suppressed incremental and maximal (but not fractional) LH pulse amplitudes in a biphasic manner. In contrast, LH peak duration was invariant until day 30 of estradiol replacement. These observations indicate that the well recognized biphasic actions of estradiol on mean serum LH concentrations can be modeled in relation to specific and time-dependent alterations in LH pulse frequency and amplitude. PMID:3818948

  4. A Gs-linked receptor maintains meiotic arrest in mouse oocytes, but luteinizing hormone does not cause meiotic resumption by terminating receptor-Gs signaling

    PubMed Central

    Norris, Rachael P.; Freudzon, Leon; Freudzon, Marina; Hand, Arthur R.; Mehlmann, Lisa M.; Jaffe, Laurinda A.

    2008-01-01

    The maintenance of meiotic prophase arrest in fully grown vertebrate oocytes depends on the activity of a Gs G-protein that activates adenylyl cyclase and elevates cAMP, and in the mouse oocyte, Gs is activated by a constitutively active orphan receptor, GPR3. To determine whether the action of luteinizing hormone (LH) on the mouse ovarian follicle causes meiotic resumption by inhibiting GPR3-Gs signaling, we examined the effect of LH on the localization of Gαs. Gs activation in response to stimulation of an exogenously expressed β2-adrenergic receptor causes Gαs to move from the oocyte plasma membrane into the cytoplasm, whereas Gs inactivation in response to inhibition of the β2-adrenergic receptor causes Gαs to move back to the plasma membrane. However, LH does not cause a change in Gαs localization, indicating that LH does not act by terminating receptor-Gs signaling. PMID:17850783

  5. Progesterone Receptor and Prostaglandins Mediate Luteinizing Hormone-Induced Changes in Messenger RNAs for ADAMTS Proteases in Theca Cells of Bovine Periovulatory Follicles

    PubMed Central

    WILLIS, ERIN L.; BRIDGES, PHILLIP J.; FORTUNE, JOANNE E.

    2017-01-01

    SUMMARY Little is known about the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of extracellular proteases in ovarian follicles of non-rodent species, particularly in theca cells. In the present study, temporal changes in the abundance of mRNA encoding four ADAMTS subtypes and hormonal regulation of mRNA encoding two subtypes were investigated in theca interna cells during the periovulatory period in cattle. Gonadotropin-releasing hormone (GnRH) was injected into animals to induce a luteinizing hormone (LH)/follicle-stimulating hormone (FSH) surge, and follicles were obtained at 0 hr post-GnRH (preovulatory) or at 6, 12, 18, or 24 hr (periovulatory). ADAMTS1, -2, -7, and -9 transcript abundance was then determined in the isolated theca interna. ADAMTS1 and -9 mRNA levels were up-regulated at 24 hr post-GnRH, whereas ADAMTS2 mRNA was higher at r12–24 hr post-GnRH and ADAMTS7 mRNA increased transiently at 12 hr post-GnRH compared to other time points. Subsequent in vitro experiments using preovulatory theca interna (0 hr post-GnRH) showed that application of LH in vitro can mimic the effects of the gonadotropin surge on mRNAs encoding ADAMTS1 and -9 and that progesterone/progesterone receptor and/or prostaglandins may regulate the levels of mRNA encoding ADAMTS1 and -9 in theca interna, downstream of the LH surge. Time- and subtype-specific changes in ADAMTS mRNA abundance in vivo, and their regulation in vitro by hormones, indicate that ADAMTS family members produced by theca cells may play important roles in follicle rupture and the accompanying tissue remodeling in cattle. PMID:27879029

  6. Aberrant luteinizing hormone-releasing hormone-stimulated adrenocorticotropic hormone secretion in a patient with pituitary hyperplasia due to primary hypothyroidism.

    PubMed

    Ban, Y; Ban, Y; Taniyama, M; Hara, H; Abe, T; Katagiri, T

    2000-08-01

    We report a patient with primary hypothyroidism associated with an aberrant ACTH response to the LH-RH test. A 40-year-old woman was admitted to our hospital displaying headache, nausea, and numbness on the left side of her face, upper limbs, and tips of her toes. Computed tomography and magnetic resonance imaging revealed a mass-like lesion in the pituitary. A high serum TSH concentration with concomitant low thyroid hormone concentrations resulted in a diagnosis of primary hypothyroidism. To exclude the possibility of a coexisting pituitary tumor including a TSH-secreting tumor, we performed dynamic TSH secretion tests. TRH testing showed an excessive, delayed TSH response, typical of primary hypothyroidism. Serum TSH decreased not only after administration of CRH, octreotide, or L-DOPA, but also after administration of LH-RH. In this case, LH-RH testing induced ACTH secretion. To determine if aberrant ACTH secretion in response to LH-RH loading is a common phenomenon in severe primary hypothyroidism, we performed the LH-RH test on 4 additional patients with pituitary enlargement due to primary hypothyroidism. Two patients demonstrated aberrant ACTH secretion in response to LH-RH loading, but the others did not. To our knowledge, this is the first report of aberrant LH-RH-stimulated ACTH secretion in primary hypothyroidism.

  7. The role of sexual steroid hormones in the direct stimulation by Kisspeptin-10 of the secretion of luteinizing hormone, follicle-stimulating hormone and prolactin from bovine anterior pituitary cells.

    PubMed

    Ezzat, A Ahmed; Saito, H; Sawada, T; Yaegashi, T; Goto, Y; Nakajima, Y; Jin, J; Yamashita, T; Sawai, K; Hashizume, T

    2010-09-01

    The aims of the present study were to clarify the effect of Kisspeptin-10 (Kp10) on the secretion of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) from bovine anterior pituitary (AP) cells and evaluate the ability of sex steroids to enhance the sensitivity of gonadotropic and lactotropic cells to Kp10. AP cells prepared from 7-week-old male calves were incubated for 12h with estradiol (E(2); 10(-8)M), progesterone (P(4); 10(-8)M), testosterone (T; 10(-8)M), or vehicle only (control), and then for 2h with Kp10 (10(-6)M). The amounts of LH, FSH and PRL released into the culture medium after the 2-h incubation period were examined. Kp10 significantly stimulated the secretion of LH from the AP cells treated with E(2) and T (P<0.05), but not from the P(4)-treated cells. In contrast, Kp10 had no effect on the secretion of FSH regardless of the steroid treatment. Kp10 significantly stimulated the secretion of PRL (P<0.05), the sexual steroid hormones having no effect. The LH- or FSH-releasing response to gonadotropin-releasing hormone (GnRH; 10(-8)M) and PRL-releasing response to thyrotropin-releasing hormone (TRH; 10(-8)M) were significantly greater than those to Kp10 (P<0.05). The present results suggest that E(2) and T, but not P(4), enhance the sensitivity of gonadotropic cells to the secretion of LH in response to Kp10. However, Kp10 had no stimulatory effect on the secretion of FSH regardless of the effect of sex steroids. Kp10 directly stimulates the secretion of PRL from the pituitary cells, and sex steroids do not enhance the sensitivity of lactotropic cells to Kp10. Furthermore, the LH- and FSH-releasing effect and the PRL-releasing effect of Kp10 are less potent than that of GnRH and TRH, respectively.

  8. Chemical synthesis of the β-subunit of human luteinizing (hLH) and chorionic gonadotropin (hCG) glycoprotein hormones.

    PubMed

    Fernández-Tejada, Alberto; Vadola, Paul A; Danishefsky, Samuel J

    2014-06-11

    Human luteinizing hormone (hLH) and human chorionic gonadotropin (hCG) are human glycoprotein hormones each consisting of two subunits, an identical α-subunit and a unique β-subunit, that form noncovalent heterodimers. Structurally, β-hCG shares a high degree of sequence similarity with β-hLH, including a common N-glycosylation site at the N-terminus but differs mainly in the presence of an extended C-terminal portion incorporating four closely spaced O-linked glycans. These glycoproteins play important roles in reproduction and are used clinically in the treatment of infertility. In addition, the role of hCG as a tumor marker in a variety of cancers has also attracted significant interest for the development of cancer vaccines. In clinical applications, these hormones are administered as mixtures of glycoforms due to limitations of biological methods in producing homogeneous samples of these glycoproteins. Using the powerful tools of chemical synthesis, the work presented herein focuses on the highly convergent syntheses of homogeneous β-hLH and β-hCG bearing model glycans at all native glycosylation sites. Key steps in these syntheses include a successful double Lansbury glycosylation en route to the N-terminal fragment of β-hCG and the sequential installation of four O-linked glycosyl-amino acid cassettes into closely spaced O-glycosylation sites in a single, high-yielding solid-supported synthesis to access the C-terminal portion of the molecule. The final assembly of the individual glycopeptide fragments involved a stepwise native chemical ligation strategy to provide the longest and most complex human glycoprotein hormone (β-hCG) as well as its closely related homologue (β-hLH) as discrete glycoforms.

  9. Influence of luteinizing hormone and adenosine 3':5'-cyclic monophosphate on the metabolism of free and esterified cholesterol in mouse Leydig-cell tumours.

    PubMed

    Moyle, W R; Jungas, R L; Greep, R O

    1973-06-01

    1. Male C57B1/6J mice bearing Leydig-cell tumours known to synthesize steroids in response to luteinizing hormone (LH) were given intravenous injections of [1,2-(3)H]cholesterol (50-100muCi per animal). Single-cell suspensions were prepared from the tumours 5-9 days after the injection of [(3)H]cholesterol and were incubated at 37 degrees C in foetal calf serum supplemented with 50mm-Tris-HCl, pH7.4. At various times after the start of incubation cells were collected by filtration of portions of the suspension and their sterols analysed. Within 10min after LH (5mug/ml) or 3':5'-cyclic AMP (20mm) was added to the cell suspensions an increased conversion of ester cholesterol into free cholesterol could be demonstrated. 2. To observe this rapid effect of LH it was necessary to incubate the cells for 60min before addition of hormone. 3. The specific radioactivity of testosterone produced was approximately equal to that of the intracellular cholesterol regardless of the presence or absence of LH. 4. The amount of free cholesterol produced in response to LH was far greater than that needed for steroid synthesis. 5. Free cholesterol, but not esterified cholesterol, was released into the incubation medium linearly with time and this release was unaffected by LH. LH may stimulate steroidogenesis in part by increasing the concentration of free cholesterol within the cell.

  10. Ovine luteinizing hormone. V. Significance of flow-through peaks observed during chromatofocusing as revealed by various methods of sample preparation and application.

    PubMed

    Grotjan, H E; Schanbacher, B D; Keel, B A

    1991-07-19

    In a previous study [Keel et al., Biol, Reprod., 36 (1987) 1102] the ovine luteinizing hormone (oLH) in pituitary extracts was chromatofocused on pH 10.5-7 gradients after equilibration in 25 mM triethylamine-HCl, pH 11.0, by gel permeation. Under these conditions, some immunoreactive oLH flowed through the columns unrestricted and this was interpreted to represent extremely basic isoforms. However, when selected flow-through peaks were re-chromatofocused, each was contaminated with other isoforms of oLH. In order to clarify this dilemma, various methods of sample preparation and application were systematically compared. Consistent with previous observations, variable amounts of the immunoreactive oLH in pituitary extracts equilibrated in triethylamine by gel permeation, dialysis, flow dialysis or ion-retardation chromatography eluted as flow-through peaks when chromatofocused. In contrast, when the ionic components in the pituitary homogenization buffer were removed by these methods as well as ultrafiltration and the proteins were applied to the resin in the elution buffer (1:45 Pharmalyte 8-10.5-HCl, pH 7.0), none of the immunoreactive oLH in pituitary extracts eluted as a flow-through peak. Thus, it appears that oLH eluting as a flow-through peak results from incomplete binding of the hormone to the chromatofocusing resin when applied in triethylamine.

  11. Thyroid hormones directly activate the expression of the human and mouse uncoupling protein-3 genes through a thyroid response element in the proximal promoter region

    PubMed Central

    2004-01-01

    The transcription of the human UCP3 (uncoupling protein-3) gene in skeletal muscle is tightly regulated by metabolic signals related to fatty acid availability. However, changes in thyroid status also modulate UCP3 gene expression, albeit by unknown mechanisms. We created transgenic mice bearing the entire human UCP3 gene to investigate the effect of thyroid hormones on human UCP3 gene expression. Treatment of human UCP3 transgenic mice with thyroid hormones induced the expression of the human gene in skeletal muscle. In addition, transient transfection experiments demonstrate that thyroid hormones activate the transcription of the human UCP3 gene promoter when MyoD and the TR (thyroid hormone receptor) were co-transfected. The action of thyroid hormones on UCP3 gene transcription is mediated by the binding of the TR to a proximal region in the UCP3 gene promoter that contains a direct repeat structure. An intact DNA sequence of this site is required for thyroid hormone responsiveness and TR binding. Chromatin immunoprecipitation assays revealed that the TR binds this element in vivo. The murine Ucp3 gene promoter was also dependent on MyoD and responsive to thyroid hormone in transient transfection assays. However, it was much less sensitive to thyroid hormone than the human UCP3 promoter. In summary, UCP3 gene transcription is activated by thyroid hormone treatment in vivo, and this activation is mediated by a TRE (thyroid hormone response element) in the proximal promoter region. Such regulation suggests a link between UCP3 gene expression and the effects of thyroid hormone on mitochondrial function in skeletal muscle. PMID:15496137

  12. Biological activities of recombinant equine luteinizing hormone/chorionic gonadotropin (eLH/CG) expressed in Sf9 and Mimic insect cell lines.

    PubMed

    Legardinier, Sébastien; Duonor-Cérutti, Martine; Devauchelle, Gérard; Combarnous, Yves; Cahoreau, Claire

    2005-02-01

    Equine luteinizing hormone (eLH) and chorionic gonadotropin (eCG) are composed of identical alpha and beta polypeptide chains, but eCG subunits are much more heavily glycosylated and sialylated. Consequently, eCG exhibits a much longer half-life than eLH in blood. Recombinant eLH/CG, expressed in Sf9 and Mimic insect cells, were compared with one another and to the natural hormones eCG and eLH. Mimic cells are stably-transformed Sf9 cells, expressing five mammalian genes encoding glycosyltransferases involved in the synthesis of complex N-carbohydrate chains. Recombinant eLH/CG expressed in Mimic cells exhibited a higher apparent molecular weight (MW) than that expressed in Sf9 cells, suggesting that its N-glycosylation was, as expected, more complete. Nevertheless, the two recombinant eLH/CG exhibited lower MW than natural eCG from pregnant mare plasma. The two eLH/CG produced in Sf9 and Mimic cells were found to be active in in vitro LH and FSH bioassays, with potencies similar to those of eCG. By contrast, they exhibited no significant in vivo bioactivity, neither in the specific follicle-stimulating hormone (FSH) assay nor in the specific eCG assay. Although recombinant eLH/CG produced in Mimic cells bears more elaborate carbohydrate chains than recombinant eLH/CG from Sf9 cells, it exhibits no significant in vivo bioactivity, probably because of insufficient terminal sialylation of its carbohydrate chains, leading to its rapid removal from blood.

  13. Prazosin blocks the glutamatergic effects of N-methyl-D-aspartic acid on lordosis behavior and luteinizing hormone secretion in the estrogen-primed female rat.

    PubMed

    Landa, A I; Cabrera, R J; Gargiulo, P A

    2006-03-01

    We have observed that intracerebroventricular (icv) injection of selective N-methyl-D-aspartic acid (NMDA)-type glutamatergic receptor antagonists inhibits lordosis in ovariectomized (OVX), estrogen-primed rats receiving progesterone or luteinizing hormone-releasing hormone (LHRH). When NMDA was injected into OVX estrogen-primed rats, it induced a significant increase in lordosis. The interaction between LHRH and glutamate was previously explored by us and another groups. The noradrenergic systems have a functional role in the regulation of LHRH release. The purpose of the present study was to explore the interaction between glutamatergic and noradrenergic transmission. The action of prazosin, an alpha1- and alpha2b-noradrenergic antagonist, was studied here by injecting it icv (1.75 and 3.5 microg/6 microL) prior to NMDA administration (1 microg/2 microL) in OVX estrogen-primed Sprague-Dawley rats (240-270 g). Rats manually restrained were injected over a period of 2 min, and tested 1.5 h later. The enhancing effect induced by NMDA on the lordosis/mount ratio at high doses (67.06 +/- 3.28, N = 28) when compared to saline controls (6 and 2 microL, 16.59 +/- 3.20, N = 27) was abolished by prazosin administration (17.04 +/- 5.52, N = 17, and 9.33 +/- 3.21, N = 20, P < 0.001 for both doses). Plasma LH levels decreased significantly only with the higher dose of prazosin (1.99 +/- 0.24 ng/mL, N = 18, compared to saline-NMDA effect, 5.96 +/- 2.01 ng/mL, N = 13, P < 0.05). Behavioral effects seem to be more sensitive to the alpha-blockade than hormonal effects. These findings strongly suggest that the facilitatory effects of NMDA on both lordosis and LH secretion in this model are mediated by alpha-noradrenergic transmission.

  14. Genome-wide association study for inhibin, luteinizing hormone, insulin-like growth factor 1, testicular size and semen traits in bovine species.

    PubMed

    Fortes, M R S; Reverter, A; Kelly, M; McCulloch, R; Lehnert, S A

    2013-07-01

    The fertility of young bulls impacts on reproduction rates, farm profit and the rate of genetic progress in beef herds. Cattle researchers and industry therefore routinely collect data on the reproductive performance of bulls. Genome-wide association studies were carried out to identify genomic regions and genes associated with reproductive traits measured during the pubertal development of Tropical Composite bulls, from 4 to 24 months of age. Data from 1 085 bulls were collected for seven traits: blood hormone levels of inhibin at 4 months (IN), luteinizing hormone following a gonadotropin releasing hormone challenge at 4 months (LH), insulin-like growth factor 1 at 6 months (IGF1), scrotal circumference at 12 months (SC), sperm motility at 18 months (MOT), percentage of normal spermatozoa at 24 months (PNS) and age at a scrotal circumference of 26 cm (AGE26, or pubertal age). Data from 729 068 single-nucleotide polymorphisms were used in the association analysis. Significant polymorphism associations were discovered for IN, IGF1, SC, AGE26 and PNS. Based on these associations, INHBE, INHBC and HELB are proposed as candidate genes for IN regulation. Polymorphisms associated with IGF1 mapped to the PLAG1 gene region, validating a reported quantitative trait locus on chromosome 14 for IGF1. The X chromosome contained most of the significant associations found for SC, AGE26 and PNS. These findings will contribute to the identification of diagnostic genetic markers and informed genomic selection strategies to assist breeding of cattle with improved fertility. Furthermore, this work provides evidence contributing to gene function annotation in the context of male fertility.

  15. Effect of a calcium channel blocker on pituitary luteinizing hormone secretion in intact and castrated male and female rats

    SciTech Connect

    Babichev, V.N.; Sidneva, L.N.; Ozol', L.Yu.

    1987-08-01

    The authors study the effect of a calcium channel blocker on leuteinizing hormone (LH) secretion through experiments on rats. LH was determined by radioimmunoassay in two or three parallel tests and in two dilutions. The effect of verapamil on the LH level in rat blood serum and the pituitary gland is shown.

  16. Activin/follistatin system in grass carp pituitary cells: - Regulation by local release of growth hormone and luteinizing hormone and its functional role in growth hormone synthesis and secretion

    PubMed Central

    Fung, Roger S. K.; Bai, Jin; Yuen, Karen W. Y.

    2017-01-01

    Gonadotrophin regulation by activin/follistatin system is well-documented, but the corresponding effect on growth hormone (GH) has not been fully characterized and with little information available in lower vertebrates, especially in fish models. In grass carp, local interactions of GH and luteinizing hormone (LH) can induce GH release and gene expression at pituitary level via autocrine/paracrine mechanisms. To shed light on the role of activin/follistatin system in GH regulation by local actions of GH and LH, grass carp activin βA and βB were cloned, shown to be single-copy genes expressed in the pituitary, and confirmed to encode activin proteins capable of transactivating promoter with activin-responsive elements. In grass carp pituitary cells, activin A and B were effective in reducing GH secretion and GH cell content with concurrent drop in GH mRNA level whereas the opposite was true for follistatin, the activin-binding protein known to neutralize the effects of endogenous activin. Treatment with activin A and B not only could suppress basal but also inhibit GH mRNA expression induced by GH and human chorionic gonadotropin (hCG), a functional analogue of LH in fish model. Apparently, down-regulation of GH mRNA by activin was mediated by reducing GH transcript stability with concurrent inhibition on GH promoter activity via the SMAD pathway. In reciprocal experiments, GH treatment was found to up-regulate activin βA, activin βB and follistatin mRNA levels in carp pituitary cells but the opposite was noted by removing endogenous GH with GH antiserum. Interestingly, parallel treatment with hCG could also inhibit basal as well as GH-induced activin βA, activin βB and follistatin gene expression. These results, as a whole, indicate that the pituitary activin/follistatin system can serve as a regulatory target for local interactions of GH and LH and contribute to GH regulation by autocrine/paracrine mechanisms in the carp pituitary. PMID:28662143

  17. Efficacy of degarelix in prostate cancer patients following failure on luteinizing hormone-releasing hormone agonist treatment: results from an open-label, multicentre, uncontrolled, phase II trial (CS27)

    PubMed Central

    Simson, Gabriele; Goble, Sandra; Persson, Bo-Eric

    2015-01-01

    Objective: To evaluate the efficacy of second-line degarelix in patients with prostate cancer (PCa) after treatment failure with a luteinizing hormone-releasing hormone (LHRH) agonist. Methods: This 1-year exploratory, multicentre, open-label phase II trial was performed in 2 patient cohorts (Cohort 1, n = 25; Cohort 2, n = 12) in Germany. Patients with castrate-resistant PCa after primary hormonal treatment received degarelix 240 mg, followed by 11 monthly maintenance doses of 80 mg. The primary endpoint was the proportion of patients with decreasing/stable prostate-specific antigen (PSA) (relative change ⩽+10% of baseline PSA) after 3 months. Results: At Month 3, the response rate (intention-to-treat, last observation carried forward analysis) was 16.7% [95% confidence interval (CI): 4.74–37.38] in Cohort 1 and 33.3% (95% CI: 9.92–65.11) in Cohort 2. The probability of completing 12 months without PSA progression was 8.8% (95% CI: 1.51–24.3) in Cohort 1 and 8.3% (95% CI: 0.5–31.1) in Cohort 2. Degarelix was well tolerated; the most frequently reported adverse events were local injection-site reactions. Conclusions: In PCa patients who failed LHRH therapy, degarelix was well tolerated and achieved a limited PSA response. Phase III trials show that disease control benefits with degarelix versus agonists are more clearly demonstrated as first-line therapy. PMID:26161141

  18. Effects of interleukin-1 beta on the steroid-induced luteinizing hormone surge: role of norepinephrine in the medial preoptic area.

    PubMed

    MohanKumar, Sheba M J; MohanKumar, P S

    2002-08-15

    Interleukin-1beta (IL-1beta), a cytokine, is known to inhibit the preovulatory surge of luteinizing hormone (LH); however, the mechanism by which it does so is unclear. This study was done to see if this effect is mediated through hypothalamic catecholamines. Adult female Sprague-Dawley rats were ovariectomized and implanted with a push-pull cannula in the medial preoptic area (MPA) of the hypothalamus. They were injected subcutaneously with 30 microg of Estradiol on the day 8 after surgery and with 2mg of Progesterone on day 10 at 1000 h. On the day of perfusion (day 10), the rats were injected with IL-1beta or its vehicle at 1300 h. Perfusate samples from the MPA and blood samples from a jugular catheter were collected from 1300 to 1800 h. Catecholamine concentrations in the perfusate were measured using high performance liquid chromatography (HPLC)-EC and LH levels in the serum using RIA. Norepinephrine release in the MPA of control rats increased significantly at 1530, 1600, and 1630 h paralelling an increase in LH at 1600 h. In contrast, IL-1beta treatment blocked the LH surge and the rise in norepinephrine release in the MPA. No changes were observed in dopamine release, both in control and IL-treated animals. These results demonstrate for the first time that IL-induced suppression of the LH surge is probably mediated through inhibition of norepinephrine release in the MPA.

  19. /sup 125/I-luteinizing hormone (LH) binding to soluble receptors from the primate (Macaca mulatta) corpus luteum: effects of ethanol exposure

    SciTech Connect

    Danforth, D.R.; Stouffer, R.L.

    1988-01-01

    In the current study, we compared the effects of ethanol on gonadotropin receptors solubilized from macaque luteal membranes to those on receptors associated with the lipid bilayer. Treatment with 1% Triton X-100 for 30 min at 4C, followed by precipitation with polyethylene glycol, resulted in recovery of 50% more binding sites for /sup 125/I-human luteinizing hormone (hLH) than were available in particulate preparations. However, the soluble receptors displayed a 3-fold lower affinity for /sup 125/I-hLH. Conditions which enhanced LH binding to particulates, i.e., 1-8% ethanol at 25C, decreased specific /sup 125/I-hLH binding to soluble receptors. Steady-state LH binding to soluble receptors during incubation at 4C was half of that observed at 25C. The presence of 8% ethanol at 4C restored LH binding to levels observed in the absence of ethanol at 25C. Thus, LH binding sites in the primate corpus luteum can be effectively solubilized with Triton X-100. The different binding characteristics of particulate and soluble receptors, including the response to ethanol exposure, suggest that the lipid environment in the luteal membrane modulates the availability and affinity of gonadotropin receptors.

  20. Analysis of human luteinizing hormone and human chorionic gonadotropin preparations of different origins by reversed-phase high-performance liquid chromatography.

    PubMed

    Almeida, B E; Oliveira, J E; Carvalho, C M; Dalmora, S L; Bartolini, P; Ribela, M T C P

    2010-09-21

    Specific reversed-phase high-performance liquid chromatography conditions are reported for the analysis of recombinant and native human luteinizing hormone (hLH) and human chorionic gonadotropin (hCG) preparations. Heterodimeric hLH, hCG and their alpha- and beta-subunits migrated with significantly different retention times (t(R)) in the following order of increasing hydrophobicity: alpha-hCG

  1. Luteinizing hormone induces ovulation via tumor necrosis factor α-dependent increases in prostaglandin F2α in a nonmammalian vertebrate

    PubMed Central

    Crespo, Diego; Goetz, Frederick W.; Planas, Josep V.

    2015-01-01

    Ovulation is induced by the preovulatory surge of luteinizing hormone (LH) that acts on the ovary and triggers the rupture of the preovulatory ovarian follicle by stimulating proteolysis and apoptosis in the follicle wall, causing the release of the mature oocyte. The pro-inflammatory cytokine tumor necrosis factor α (TNFα) and prostaglandin (PG) F2α (PGF2α) are involved in the control of ovulation but their role mediating the pro-ovulatory actions of LH is not well established. Here we show that Lh induces PGF2α synthesis through its stimulation of Tnfα production in trout, a primitive teleost fish. Recombinant trout Tnfα (rTnfα) and PGF2α recapitulate the stimulatory in vitro effects of salmon Lh (sLh) on contraction, proteolysis and loss of cell viability in the preovulatory follicle wall and, finally, ovulation. Furthermore, all pro-ovulatory actions of sLh are blocked by inhibition of Tnfα secretion or PG synthesis and all actions of rTnfα are blocked by PG synthesis inhibitors. Therefore, we provide evidence that the Tnfα–dependent increase in PGF2α production is necessary for the pro-ovulatory actions of Lh. The results from this study shed light onto the mechanisms underlying the pro-ovulatory actions of LH in vertebrates and may prove important in clinical assessments of female infertility. PMID:26374476

  2. A randomized prospective study to assess the effect of the use of home urinary luteinizing hormone detection on the efficiency of donor insemination.

    PubMed

    Robinson, J N; Lockwood, G M; Dalton, J D; Franklin, P A; Farr, M M; Barlow, D H

    1992-01-01

    A study was carried out to establish whether the use of home urinary luteinizing hormone (LH) detection to predict ovulation could decrease the number of clinic visits required for the management of a donor insemination (DI) cycle, and thus optimize use of clinic resources without adversely affecting pregnancy rates. This was a randomized prospective study carried out at a donor insemination clinic in Oxford, England. Fifty-six patients participated in the trial; 27 used home urinary ovulation detection for a total of 111 cycles and 29 had a total of 123 DI cycles managed by routine clinical methods. There was a significant reduction in the number of visits per cycle (P less than 0.001) if home kits for detection of ovulation were used. There was no significant difference in the monthly fecundity or cumulative conception rates. We conclude that the use of home urinary LH detection in donor insemination can reduce patient attendance at the clinic and optimize the use of medical resources without adversely affecting pregnancy rates.

  3. The GABA(B) antagonist CGP 52432 attenuates the stimulatory effect of the GABA(B) agonist SKF 97541 on luteinizing hormone secretion in the male sheep.

    PubMed

    Jackson, Gary L; Kuehl, David

    2002-05-01

    The objectives of this study were to determine if the gamma-aminobutyric acid (GABA)(B) agonist, 3-aminopropyl (methyl) phosphinic acid (SKF97541), would increase luteinizing hormone (LH) secretion when infused by microdialysis into the medial basal hypothalamus (MBH) of the castrated ram, and to determine if the action of SKF97541 would be attenuated by co-infusion of the GABA(B) antagonist CGP52432. Initial experiments established that infusion of SKF alone, at concentrations as low as 5 microM, increased mean LH, LH pulse amplitude, and in some cases, pulse interval. In the last experiment, animals were treated with artificial cerebrospinal fluid (CSF) alone, SKF alone (30 microM), 3-[[(3, 4-dichlorophenol) methyl] amino] propyl] diethoxymethyl) phosphinic acid (CGP) alone (500 microM), or SKF plus CGP. SKF increased both mean LH and LH pulse amplitude as compared with CSF. CGP alone had no significant effect on LH, but it attenuated the effect of SKF on mean LH. These observations indicate that the stimulatory effects of GABA(B) agonists on LH pulse patterns are mediated through GABA(B) receptors and provide further evidence that GABA(B) receptors located in the MBH can regulate pulsatile GnRH-LH release.

  4. Sexually dimorphic expression of estrogen receptor β in the anteroventral periventricular nucleus of the rat preoptic area: Implication in luteinizing hormone surge

    PubMed Central

    Orikasa, Chitose; Kondo, Yasuhiko; Hayashi, Shinji; McEwen, Bruce S.; Sakuma, Yasuo

    2002-01-01

    Striking sex difference was detected in the expression of estrogen receptor (ER) β mRNA and protein by nonisotopic in situ hybridization and immunohistochemistry in the anteroventral periventricular nucleus (AVPV) of the rat preoptic area. In females more than in males, a significantly larger number of ERβ mRNA-positive cells were visualized in the medial-most portion of the AVPV within 50 μm from the ependymal lining of the third ventricle. Rats of 7, 14, 21, 35, and 60 days of age (d 1 = day of birth) showed the sex difference. Orchidectomy of male neonates or estrogen treatment of female pups reversed the brain phenotype when examined on d 14. In the AVPV of adult females, ERα immunoreactivity colocalized in 83% of ERβ mRNA-positive cells. Tyrosine hydroxylase immunoreactivity colocalized in 18% of ERβ immunoreactive cells in d 21 females. Infusion of an ERβ antisense oligonucleotide into the third ventricle in the vicinity of the AVPV resulted in significantly longer days of successive estrus and a 50% reduction in the number of ERβ-immunoreactive cells in the AVPV. These findings provide support for the hypothesis that activation of ERβ in the AVPV is an important regulatory event in the female-typical induction of luteinizing hormone surge by estrogen. PMID:11854469

  5. Luteinizing Hormone Reduces the Activity of the NPR2 Guanylyl Cyclase in Mouse Ovarian Follicles, Contributing to the Cyclic GMP Decrease that Promotes Resumption of Meiosis in Oocytes

    PubMed Central

    Robinson, Jerid W.; Zhang, Meijia; Shuhaibar, Leia C.; Norris, Rachael P.; Geerts, Andreas; Wunder, Frank; Eppig, John J.; Potter, Lincoln R.; Jaffe, Laurinda A.

    2012-01-01

    In preovulatory ovarian follicles of mice, meiotic prophase arrest in the oocyte is maintained by cyclic GMP from the surrounding granulosa cells that diffuses into the oocyte through gap junctions. The cGMP is synthesized in the granulosa cells by the transmembrane guanylyl cyclase natriuretic peptide receptor 2 (NPR2) in response to the agonist C-type natriuretic peptide (CNP). In response to luteinizing hormone (LH), cGMP in the granulosa cells decreases, and as a consequence, oocyte cGMP decreases and meiosis resumes. Here we report that within 20 minutes, LH treatment results in decreased guanylyl cyclase activity of NPR2, as determined in the presence of a maximally activating concentration of CNP. This occurs by a process that does not reduce the amount of NPR2 protein. We also show that by a slower process, first detected at 2 hours, LH decreases the amount of CNP available to bind to the receptor. Both of these LH actions contribute to decreasing cGMP in the follicle, thus signaling meiotic resumption in the oocyte. PMID:22546688

  6. Morphometric analysis of the folliculostellate cells and luteinizing hormone gonadotropic cells of the anterior pituitary of the men during the aging process.

    PubMed

    Čukuranović Kokoris, Jovana; Jovanović, Ivan; Pantović, Vukica; Krstić, Miljan; Stanojković, Milica; Milošević, Verica; Ugrenović, Slađana; Stojanović, Vesna

    2017-02-01

    The aim of this research was to quantify the changes in the morphology and density of the anterior pituitary folliculostellate (FS) and luteinizing hormone (LH) cells. Material was tissue of the pituitary gland of the 14 male cadavers. Tissue slices were immunohistochemically stained with monoclonal anti-LH antibody and polyclonal anti-S100 antibody for the detection of LH and FS cells, respectively. Digital images of the stained slices were afterwards morphometrically analyzed by ImageJ. Results of the morphometric analysis showed significant increase of the FS cells volume density in cases older than 70 years. Volume density of the LH cells did not significantly change, whereas their area significantly increased with age. Nucleocytoplasmic ratio of the LH cells gradually decreased and became significant after the age of 70. Finally, volume density of the FS cell significantly correlated with LH cells area and nucleocytoplasmic ratio. From all above cited, we concluded that in men, density and size of the FS cells increase with age. Long-term hypertrophy of the LH cells results in their functional decline after the age of 70. Strong correlation between FS cells and LH cells morphometric parameters might point to age-related interaction between these two cell groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. 11β-hydroxysteroid dehydrogenase types 1 and 2 in postnatal development of rat testis: gene expression, localization and regulation by luteinizing hormone and androgens.

    PubMed

    Zhou, Hong-Yu; Chen, Xin-Xin; Lin, Han; Fei, Ai-Li; Ge, Ren-Shan

    2014-01-01

    11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and type 2 (11β-HSD2) are expressed in rat testis, where they regulate the local concentrations of glucocorticoids. Here, we investigated the expression and localization of 11β-HSD in rat testis during postnatal development, and the regulation of these genes by luteinizing hormone (LH) and androgens. mRNA and protein levels were analyzed by quantitative real-time-polymerase chain reaction and western blotting, respectively, in testes collected from rats at postnatal day (PND) 7, 14, 21, 35, and 90, and from rats treated with LH, 7α-methyl-19-nortestosterone (MENT) and testosterone at PND 21 and PND 90. Immunohistochemical staining was used to identify the localization of the 11β-HSD in rat testis at PND 7, 14, and 90. We found that 11β-HSD1 expression was restricted to the interstitial areas, and that its levels increased during rat testis development. In contrast, whereas 11β-HSD2 was expressed in both the interstitial areas and seminiferous tubules at PND 7, it was present only in the interstitial areas at PND 90, and its levels declined during testicular development. Moreover, 11β-HSD1 mRNA was induced by LH in both the PND 21 and 90 testes and by MENT at PND 21, whereas 11β-HSD2 mRNA was induced by testosterone and MENT in the PND 21 testis and by LH in the PND 90 testis. In conclusion, our study indicates that the 11β-HSD1 and 11β-HSD2 genes have distinct patterns of spatiotemporal expression and hormonal regulation during postnatal development of the rat testis.

  8. Expression of receptors for luteinizing hormone, gastric-inhibitory polypeptide, and vasopressin in normal adrenal glands and cortisol-secreting adrenocortical tumors in dogs.

    PubMed

    Galac, S; Kars, V J; Klarenbeek, S; Teerds, K J; Mol, J A; Kooistra, H S

    2010-07-01

    Hypercortisolism caused by an adrenocortical tumor (AT) results from adrenocorticotropic hormone (ACTH)-independent hypersecretion of glucocorticoids. Studies in humans demonstrate that steroidogenesis in ATs may be stimulated by ectopic or overexpressed eutopic G protein-coupled receptors. We report on a screening of 23 surgically removed, cortisol-secreting ATs for the expression of receptors for luteinizing hormone (LH), gastric-inhibitory polypeptide (GIP), and vasopressin (V(1a), V(1b), and V(2)). Normal adrenal glands served as control tissues. Abundance of mRNA for these receptors was quantified using quantitative polymerase chain reaction (QPCR), and the presence and localization of these receptors were determined by immunohistochemistry. In both normal adrenal glands and ATs, mRNA encoding for all receptors was present, although the expression abundance of the V(1b) receptor was very low. The mRNA expression abundance for GIP and V(2) receptors in ATs were significantly lower (0.03 and 0.01, respectively) than in normal adrenal glands. The zona fasciculata of normal adrenal glands stained immunonegative for the GIP receptor. In contrast, islands of GIP receptor-immunopositive cells were detected in about half of the ATs. The zona fasciculata of both normal adrenal glands and AT tissue were immunopositive for LH receptor; in ATs in a homogenous or heterogenous pattern. In normal adrenal glands, no immunolabeling for V(1b)R and V(2) receptor was present, but in ATs, V(2) receptor-immunopositive cells were detected. In conclusion, QPCR analysis did not reveal overexpression of LH, GIP, V(1a), V(1b), or V(2) receptors in the ATs. However, the ectopic expression of GIP and V(2) receptor proteins in tumorous zona fasciculata tissue may play a role in the pathogenesis of canine cortisol-secreting ATs.

  9. Plasma levels of follicle-stimulating and luteinizing hormones during the reproductive cycle of wild and cultured Senegalese sole (Solea senegalensis).

    PubMed

    Chauvigné, François; Fatsini, Elvira; Duncan, Neil; Ollé, Judith; Zanuy, Silvia; Gómez, Ana; Cerdà, Joan

    2016-01-01

    The intensive culture of the Senegalese sole (Solea senegalensis) is hampered by the low or null fertilization rates exhibited by the first generation (F1) of reared males. To investigate the regulation of the reproductive processes in this species by the pituitary gonadotropins follicle-stimulating and luteinizing hormones (Fsh and Lh, respectively), we developed a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) for Lh measurements. Quantification of the Fsh and Lh plasma levels in cultured sole using the Lh ELISA developed here, and a previously developed ELISA for Fsh, indicated that in both males and females circulating Fsh steadily increased during autumn and winter and prior to the major spawning in spring, whereas an Lh surge occurred specifically during spawning. The increase in Fsh was associated with a rise of plasma levels of the steroid hormones testosterone (T), 11-ketotestosterone (11-KT) and estradiol-17β (E2), but that of Lh was concomitant with a strong decline of the levels of E2 in females and of 11-KT in males, possibly reflecting a rapid steroidogenic shift promoting the final maturation of gametes. Comparison of the plasma levels of gonadotropins and steroids between wild and F1 fish during autumn and spring revealed that F1 males showed significantly lower plasma Lh titres compared to wild males, whereas the levels of T and 11-KT were similar or more elevated in the F1 fish. These data suggest that an impaired Lh secretion during spawning, and perhaps altered Lh-mediated mechanisms in the testis, may be underlying causes for the low reproductive performance of Senegalese sole F1 males.

  10. Phenobarbital blockade of the preovulatory luteinizing hormone surge: association with phase-advanced circadian clock and altered suprachiasmatic nucleus Period1 gene expression

    PubMed Central

    Legan, Sandra J.; Donoghue, Kathleen M.; Franklin, Kathleen M.; Duncan, Marilyn J.

    2009-01-01

    The suprachiasmatic nucleus (SCN) controls the timing of the preovulatory luteinizing hormone (LH) surge in laboratory rodents. Barbiturate administration during a critical period on proestrus delays the surge and prolongs the estrous cycle 1 day. Because a nonphotic timing signal (zeitgeber) during the critical period that phase advances activity rhythms can also induce the latter effect, we hypothesized that barbiturates delay the LH surge by phase-advancing its circadian timing signal beyond the critical period. In experiment 1, locomotor rhythms and estrous cycles were monitored in hamsters for 2–3 wk preinjection and postinjection of vehicle or phenobarbital and after transfer to darkness at zeitgeber time (ZT) 6 on proestrus. Phenobarbital delayed estrous cycles in five of seven hamsters, which exhibited phase shifts that averaged twofold greater than those exhibited by vehicle controls or phenobarbital-injected hamsters with normal cycles. Experiment 2 used a similar protocol, but injections were at ZT 5, and blood samples for LH determination were collected from 1200 to 1800 on proestrus and the next day via jugular cannulae inserted the day before proestrus. Phenobarbital delayed the LH surge 1 day in all six hamsters, but it occurred at an earlier circadian time, supporting the above hypothesis. Experiment 3 investigated whether phenobarbital, like other nonphotic zeitgebers, suppresses SCN Period1 and Period2 transcription. Two hours postinjection, phenobarbital decreased SCN expression of only Period1 mRNA, as determined by in situ hybridization. These results suggest that phenobarbital advances the SCN pacemaker, governing activity rhythms and hormone release in part by decreasing its Period1 gene expression. PMID:19297538

  11. GLP-1R Signaling Directly Activates Arcuate Nucleus Kisspeptin Action in Brain Slices but Does not Rescue Luteinizing Hormone Inhibition in Ovariectomized Mice During Negative Energy Balance.

    PubMed

    Heppner, Kristy M; Baquero, Arian F; Bennett, Camdin M; Lindsley, Sarah R; Kirigiti, Melissa A; Bennett, Baylin; Bosch, Martha A; Mercer, Aaron J; Rønnekleiv, Oline K; True, Cadence; Grove, Kevin L; Smith, M Susan

    2017-01-01

    Kisspeptin (Kiss1) neurons in the hypothalamic arcuate nucleus (ARC) are key components of the hypothalamic-pituitary-gonadal axis, as they regulate the basal pulsatile release of gonadotropin releasing hormone (GnRH). ARC Kiss1 action is dependent on energy status, and unmasking metabolic factors responsible for modulating ARC Kiss1 neurons is of great importance. One possible factor is glucagon-like peptide 1 (GLP-1), an anorexigenic neuropeptide produced by brainstem preproglucagon neurons. Because GLP fiber projections and the GLP-1 receptor (GLP-1R) are abundant in the ARC, we hypothesized that GLP-1R signaling could modulate ARC Kiss1 action. Using ovariectomized mice, we found that GLP-producing fibers come in close apposition with ARC Kiss1 neurons; these neurons also contain Glp1r mRNA. Electrophysiological recordings revealed that liraglutide (a long-acting GLP-1R agonist) increased action potential firing and caused a direct membrane depolarization of ARC Kiss1 cells in brain slices. We determined that brainstem preproglucagon mRNA is decreased after a 48-h fast in mice, a negative energy state in which ARC Kiss1 expression and downstream GnRH/luteinizing hormone (LH) release are potently suppressed. However, activation of GLP-1R signaling in fasted mice with liraglutide was not sufficient to prevent LH inhibition. Furthermore, chronic central infusions of the GLP-1R antagonist, exendin(9-39), in ad libitum-fed mice did not alter ARC Kiss1 mRNA or plasma LH. As a whole, these data identify a novel interaction of the GLP-1 system with ARC Kiss1 neurons but indicate that CNS GLP-1R signaling alone is not critical for the maintenance of LH during fasting or normal feeding.

  12. Influence of luteinizing hormone and adenosine 3′:5′-cyclic monophosphate on the metabolism of free and esterified cholesterol in mouse Leydig-cell tumours

    PubMed Central

    Moyle, William R.; Jungas, Robert L.; Greep, Roy O.

    1973-01-01

    1. Male C57B1/6J mice bearing Leydig-cell tumours known to synthesize steroids in response to luteinizing hormone (LH) were given intravenous injections of [1,2-3H]cholesterol (50–100μCi per animal). Single-cell suspensions were prepared from the tumours 5–9 days after the injection of [3H]cholesterol and were incubated at 37°C in foetal calf serum supplemented with 50mm-Tris–HCl, pH7.4. At various times after the start of incubation cells were collected by filtration of portions of the suspension and their sterols analysed. Within 10min after LH (5μg/ml) or 3′:5′-cyclic AMP (20mm) was added to the cell suspensions an increased conversion of ester cholesterol into free cholesterol could be demonstrated. 2. To observe this rapid effect of LH it was necessary to incubate the cells for 60min before addition of hormone. 3. The specific radioactivity of testosterone produced was approximately equal to that of the intracellular cholesterol regardless of the presence or absence of LH. 4. The amount of free cholesterol produced in response to LH was far greater than that needed for steroid synthesis. 5. Free cholesterol, but not esterified cholesterol, was released into the incubation medium linearly with time and this release was unaffected by LH. LH may stimulate steroidogenesis in part by increasing the concentration of free cholesterol within the cell. PMID:16742799

  13. Consequences of elevated luteinizing hormone on diverse physiological systems: use of the LHbetaCTP transgenic mouse as a model of ovarian hyperstimulation-induced pathophysiology.

    PubMed

    Mann, Rachel J; Keri, Ruth A; Nilson, John H

    2003-01-01

    Chronically elevated luteinizing hormone (LH) induces significant pathology in the LHbetaCTP transgenic mouse model, which uses the bovine gonadotropin alpha (alpha)-subunit promoter to direct transgene expression specifically to gonadotropes in the anterior pituitary. Previously, it was shown that female LHbetaCTP mice are infertile due to anovulation, develop granulosa cell tumors, and undergo precocious puberty from elevated LH and steroid hormones that fail to completely repress the alpha-subunit promoter. This chapter will discuss recent studies that further elucidate the impact of chronically elevated LH on diverse physiological systems. Granulosa cell tumors induced by elevated LH are strain dependent and prevented when transgenics are treated with human chorionic gonadotropin (hCG) surges. A granulosa cell tumor-associated transcriptome is generated, revealing several possible gene candidates for ovarian granulosa cell tumorigenesis. Primordial follicles in LHbetaCTP transgenics become depleted and oocytes exhibit increased rates of meiotic segregation defects, although meiotic competency is acquired normally. Anovulation can be rescued in transgenics by superovulation, though pregnancy fails at midgestation due to maternal factors. Uterine receptivity defects prevent implantation of normal embryos following induction of pseuodpregnancy. Transgenics develop Cushing-like adrenocortical hyperfunction with increased corticosterone production following induction of adrenal LH receptor expression. Elevated LH acts as a tumor promoter in the gonads and the adrenal gland, when expressed in conjunction with the inhibin-alpha SV40 transgene. Finally, chronic elevated LH promotes mammary tumorigenesis. The understanding of multiple clinical pathologies--including ovarian cancer, perimenopausal reproductive aging, premature ovarian failure, polycystic ovarian syndrome, Cushing's syndrome, and breast cancer--may be enhanced through further study of this useful

  14. GLP-1R Signaling Directly Activates Arcuate Nucleus Kisspeptin Action in Brain Slices but Does not Rescue Luteinizing Hormone Inhibition in Ovariectomized Mice During Negative Energy Balance

    PubMed Central

    Heppner, Kristy M.; Baquero, Arian F.; True, Cadence; Grove, Kevin L.

    2017-01-01

    Abstract Kisspeptin (Kiss1) neurons in the hypothalamic arcuate nucleus (ARC) are key components of the hypothalamic-pituitary-gonadal axis, as they regulate the basal pulsatile release of gonadotropin releasing hormone (GnRH). ARC Kiss1 action is dependent on energy status, and unmasking metabolic factors responsible for modulating ARC Kiss1 neurons is of great importance. One possible factor is glucagon-like peptide 1 (GLP-1), an anorexigenic neuropeptide produced by brainstem preproglucagon neurons. Because GLP fiber projections and the GLP-1 receptor (GLP-1R) are abundant in the ARC, we hypothesized that GLP-1R signaling could modulate ARC Kiss1 action. Using ovariectomized mice, we found that GLP-producing fibers come in close apposition with ARC Kiss1 neurons; these neurons also contain Glp1r mRNA. Electrophysiological recordings revealed that liraglutide (a long-acting GLP-1R agonist) increased action potential firing and caused a direct membrane depolarization of ARC Kiss1 cells in brain slices. We determined that brainstem preproglucagon mRNA is decreased after a 48-h fast in mice, a negative energy state in which ARC Kiss1 expression and downstream GnRH/luteinizing hormone (LH) release are potently suppressed. However, activation of GLP-1R signaling in fasted mice with liraglutide was not sufficient to prevent LH inhibition. Furthermore, chronic central infusions of the GLP-1R antagonist, exendin(9–39), in ad libitum–fed mice did not alter ARC Kiss1 mRNA or plasma LH. As a whole, these data identify a novel interaction of the GLP-1 system with ARC Kiss1 neurons but indicate that CNS GLP-1R signaling alone is not critical for the maintenance of LH during fasting or normal feeding. PMID:28144621

  15. Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.

    PubMed Central

    Veldhuis, J D; Rogol, A D; Samojlik, E; Ertel, N H

    1984-01-01

    We have tested the participation of endogenous opiate pathways in the negative feedback actions of gonadal steroids on pulsatile properties of luteinizing (LH) hormone release in normal men. To this end, sex steroid hormones were infused intravenously at dosages that under steady state conditions selectively suppressed either the frequency or the amplitude of the pulsatile LH signal. The properties of pulsatile LH secretion were assessed quantitatively by computerized analysis of LH series derived from serial blood sampling over 12 h of observation. When the pure (nonaromatizable) androgen, 5-alpha-dihydrotestosterone, was infused continuously for 108 h at the blood production rate of testosterone, we were able to achieve selective inhibition of LH pulse frequency akin to that observed in experimental animals after low-dosage androgen replacement. Under these conditions, serum concentrations of testosterone and estradiol-17 beta did not change significantly, but serum 5 alpha-dihydrotestosterone concentrations increased approximately two- to threefold, with a corresponding increase in levels of its major metabolite, 5 alpha-androstan-3 alpha, 17 beta-diol. In separate experiments, the infusion of estradiol-17 beta at its blood production rate over a 4.5-d interval selectively suppressed LH pulse amplitude without influencing LH pulse frequency. Estrogen infusion increased serum estradiol-17 beta levels approximately twofold without significantly altering blood androgen concentrations. We then used these schedules of selective androgen or estrogen infusion to investigate the participation of endogenous opiates in the individual inhibitory feedback actions of pure androgen or estrogen on pulsatile LH release by administering a potent and specific opiate-receptor antagonist, naltrexone, during the infusions. Our observations indicate that, despite the continuous infusion of a dosage of 5 alpha-dihydrotestosterone that significantly suppresses LH pulse frequency, co

  16. Relationship between the onset of oestrus, the preovulatory surge in luteinizing hormone and ovulation following oestrous synchronization and superovulation of farmed red deer (Cervus elaphus).

    PubMed

    Asher, G W; Fisher, M W; Jabbour, H N; Smith, J F; Mulley, R C; Morrow, C J; Veldhuizen, F A; Langridge, M

    1992-09-01

    The timing of ovulation relative to the onset of oestrus and the preovulatory surge in luteinizing hormone (LH) was studied in red deer following treatments to synchronize oestrus and induce either a monovulatory or superovulatory response. Mature hinds (n = 36) were allocated randomly to two mating groups (n = 16 + 20), with respective treatments staggered by 4 weeks during the 1990 rut (March-April). Each hind was treated with an intravaginal controlled internal drug releasing (CIDR)-type S device for 14 days. Treatments to induce a monovulatory response included CIDR device alone (treatment A; n = 4 + 8) and additional injection of 200 iu pregnant mares' serum gonadotrophin (PMSG) at device removal (treatment B; n = 4 + 4). Treatments to induce a superovulatory response included injections of 200 iu PMSG and 0.5 units ovine follicle-stimulating hormone (FSH) at about time of removal of CIDR devices (treatment C; n = 4 + 4) and further treatment with gonadotrophin-releasing hormone (GnRH) analogue 18 h after removal of CIDR devices (treatment D; n = 4 + 4). The hinds were run with crayon-harnessed stags from insertion of CIDR devices (12 March or 9 April) and blood samples were taken every second day to determine plasma progesterone. Further blood samples were collected for determination of plasma LH and progesterone via indwelling jugular cannulae every 2 h for 72 h from removal of CIDR devices. Hinds were allocated randomly to an initial ovarian examination by laparoscopy at either 16 or 20 h (A and B), or 12 or 16 h (C and D) after the onset of oestrus, with laparoscopy repeated at intervals of 8 h until either ovulation was recorded (A and B), or for four successive occasions (C and D). All hinds received cloprostenol injections 15 days after device removal. A total of 28 hinds (78%) exhibited oestrus and a preovulatory LH surge, with mean (+/- SEM) times to onset of oestrus of 44.6 +/- 1.0 h (A; n = 7), 37.4 +/- 2.0 h (B; n = 7), 16.3 +/- 1.7 h (C; n = 6) or

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

    SciTech Connect

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

    1990-12-01

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

  18. Effects of Ghrelin on Sexual Behavior and Luteinizing Hormone Beta-subunit Gene Expression in Male Rats

    PubMed Central

    Babaei-Balderlou, Farrin; Khazali, Homayoun

    2016-01-01

    Background: The hormones of hypothalamo-pituitary-gonadal (HPG) axis have facilitative effects on reproductive behavior in mammals. Ghrelin as a starvation hormone has an inhibitory effect on HPG axis’ function. Hence, it is postulated that ghrelin may reduce the sexual behavior through inhibiting of HPG axis. The aim of this study was to examine the effects of ghrelin and its antagonist, [D-Lys3 ]-GHRP-6, on sexual behavior and LH beta-subunit gene expression in male rats. Methods: In this experimental study, 128 male Wistar rats were divided into two groups. Each group was further subdivided into eight subgroups (n=8 rats/subgroup) including the animals that received saline, ghrelin (2, 4 or 8 nmol), [D-Lys3 ]-GHRP-6 (5 or 10 nmol) or co-administration of ghrelin (4 nmol) and [D-Lys3 ]-GHRP-6 (5 or 10 nmol) through the stereotaxically implanted cannula into the third cerebral ventricle. The sexual behavior of male rats encountering with females and the hypo-physeal LH beta-subunit gene expression were evaluated at two different groups. Data were analyzed by ANOVA and p<0.05 was considered statistically significant. Results: Ghrelin injection (4 and 8 nmol) significantly (p<0.01) increased the latencies to the first mount, intromission and ejaculation as well as the post-ejaculatory interval. Also, 4 and 8 nmol ghrelin significantly (p<0.05) increased the number of mount and decreased the number of ejaculation. In co-administrated groups, [D-Lys3 ]-GHRP-6 antagonized the effects of ghrelin. Ghrelin injection (4 and 8 nmol) reduced the LH beta-subunit gene expression while pretreatment with [D-Lys3 ]-GHRP-6 improved the gene expression. Conclusion: Ghrelin decreased the sexual behavior and LH beta-subunit gene expression in male rats, whereas [D-Lys3 ]-GHRP-6 antagonizes these effects. PMID:27141463

  19. Primary and secondary structural determinants in the receptor binding sequence. beta. -(38-57) from human luteinizing hormone

    SciTech Connect

    Keutmann, H.T.; Charlesworth, M.C.; Kitzmann, K.; Mason, K.A.; Johnson, L.; Ryan, R.J.

    1988-12-13

    The intercysteine loop sequence 38-57 in the ..beta.. subunit has been shown to be a determinant for expression of biological activity in human lutropin (hLH) and choriogonadotropin (hCG). Together with other sequences, the 38-57 region may contribute to a multicomponent receptor binding domain in hLH/hCG. Because the structural features influencing activity in this important region are not easy to evaluate in the full-length subunit, the authors have used analogues of hLH..beta..-(38-57) prepared by solid-phase synthesis. The peptides were tested for inhibition of /sup 125/I-labeled hCG binding to rat ovarian membrane receptors. Secondary structure was analyzed by circular dichroism (CD) and by reactivity with antibodies to the native 38-57 peptide. An analogue lacking the 38-57 disulfide linkage retained 20% receptor binding and full immunoreactivity. Far-ultraviolet CD profiles were essentially identical with those of the disulfide-intact peptide; a transition from 10% to 30% ..cap alpha..-helix in 90% trifluoroethanol was characteristic of both. The peptide thus appears not to require the disulfide bridge to retain a looped conformation with amphipathic secondary structure. An essential positive charge at position 43 was shown by complete loss of activity upon substitution of Asp or Ala for the Arg found in all known species of LH. These results indicate that the 38-57 sequence is a relatively rigid and structurally autonomous region, not merely a series of residues constrained passively into a loop by a disulfide linkage. It includes segments of ordered structure, probably including both amphipathic helical and turn sequences. Evidence from studies of other hormones suggests that this region may be important to binding and specificity in the glycoprotein hormones as a group.

  20. Relative effectiveness of carp pituitary extract, luteinizing hormone releasing hormone analog LHRHa injections and LHRHa implants for producing hybrid catfish fry

    USDA-ARS?s Scientific Manuscript database

    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...

  1. Post-Natal Dynamic Changes in Circulating Follicle-Stimulating Hormone, Luteinizing Hormone, Immunoreactive Inhibin, Progesterone, Testosterone and Estradiol-17β in Thoroughbred Colts until 6 Months of Age

    PubMed Central

    DHAKAL, Pramod; TSUNODA, Nobuo; NAKAI, Rie; NAGAOKA, Kentaro; NAMBO, Yasuo; SATO, Fumio; TANIYAMA, Hiroyuki; TAYA, Kazuyoshi

    2011-01-01

    The aim of present study was to clarify the post-natal profile of follicle-stimulating hormone (FSH), luteinizing hormone (LH), immunoreactive (ir)-inhibin, progesterone, testosterone, and estradiol-17β, and their relationships in Thoroughbred colts. Six hundred and thirty-six colts were used for the study. Single plasma samples from each animal were harvested from the blood drawn through jugular venipuncture. The subjects were born with high amounts of progesterone, testosterone, and estradiol-17β, all of which dropped significantly and remained at lower levels till the end of 6 months. FSH decreased transiently after birth until day 12 and then gradually increased to peak at day 100 which then maintained in lesser levels towards the end of the studied period. LH was highest during birth which decreased until day 26 and then increased slowly to sub-birth levels up to day 90. Animals were born with high amounts of ir-inhibin. It dropped slowly and halved by day 20 and then decreased towards rest of the studied period. The increase in FSH is negatively correlated with the declining ir-inhibin levels. The early increase in FSH can be the indication of early post-natal maturation of the hypothalamic pituitary testicular axis that ultimately might be responsible for priming the testes for future development. PMID:24833982

  2. Infertility in Female Mice with a Gain-of-Function Mutation in the Luteinizing Hormone Receptor Is Due to Irregular Estrous Cyclicity, Anovulation, Hormonal Alterations, and Polycystic Ovaries1

    PubMed Central

    Hai, Lan; McGee, Stacey R.; Rabideau, Amanda C.; Paquet, Marilène; Narayan, Prema

    2015-01-01

    The luteinizing hormone receptor, LHCGR, is essential for fertility in males and females, and genetic mutations in the receptor have been identified that result in developmental and reproductive defects. We have previously generated and characterized a mouse model (KiLHRD582G) for familial male-limited precocious puberty caused by an activating mutation in the receptor. We demonstrated that the phenotype of the KiLHRD582G male mice is an accurate phenocopy of male patients with activating LHCGR mutations. In this study, we observed that unlike women with activating LHCGR mutations who are normal, female KiLHRD582G mice are infertile. Mice exhibit irregular estrous cyclicity, anovulation, and precocious puberty. A temporal study from 2–24 wk of age indicated elevated levels of progesterone, androstenedione, testosterone, and estradiol and upregulation of several steroidogenic enzyme genes. Ovaries of KiLHRD582G mice exhibited significant pathology with the development of large hemorrhagic cysts as early as 3 wk of age, extensive stromal cell hyperplasia and hypertrophy with luteinization, numerous atretic follicles, and granulosa cell tumors. Ovulation could not be rescued by the addition of exogenous gonadotropins. The body weights of the KiLHRD582G mice were higher than wild-type counterparts, but there was no increase in the body fat composition or metabolic abnormalities such as impaired glucose tolerance and insulin resistance. These studies demonstrate that activating LHCGR mutations do not produce the same phenotype in female mice as in humans and clearly illustrate species differences in the expression and regulation of LHCGR in the ovary, but not in the testis. PMID:26040673

  3. Testicular adrenal rests: evidence for luteinizing hormone receptors and for distinct types of testicular nodules differing for their autonomization.

    PubMed

    Benvenga, S; Smedile, G; Lo Giudice, F; Trimarchi, F

    1999-09-01

    We report one patient with 21-hydroxylase deficiency and associated bilateral macro-orchidism caused by nodular hyperplasia of testicular adrenal rests (TAR). The boy, referred to us when 10 years old, was born with bilateral cryptorchidism that was treated unsuccessfully with i.m. injections of human chorionic gonadotropin (hCG) and later on with orchidopexy. He was treated with oral dexamethasone (0.625 mg per day) for the following 13 years. After one year, there was a marked reduction in steroid hormone levels (17-hydroxyprogesterone (17-OH P) from 27.2 to 1.2 nmol/l, testosterone from >104 to 4.8 nmol/l, estradiol (E(2)) from 481 to 33 pmol/l). After the same period of time, both testicular volume and nodularity decreased: from 45 to 18 ml and from numerous to four nodules in the right testis, and from 40 to 13 ml and from numerous to three nodules in the left testis. At the third year, there were transient increases in serum gonadotropins, testicular volume (right testis = 25 ml, left testis = 20 ml) and steroid hormones, including cortisol (serum ACTH and dehydroepiandrosterone sulfate remained suppressed). At the fourth year of follow-up, there were still four nodules in the right testis and three in the left testis. The LH-dependency (which implies possession of LH/hCG receptors) of these nodules was also substantiated by their steroidogenic response to an acute i.m. hCG test. An exogenous ACTH stimulation test increased serum 17-OH P and cortisol. Since these nodules, unlike the majority of those present initially, were not suppressed by the corticosteroid therapy and since they were not detected when the patient returned for control at 23 years of age, they had partial autonomy from ACTH. At 23 years of age, the patient had a single nodule in the right testis (right testis volume = 13 ml, left testis volume = 10 ml), which should have accounted for the consistent difference in size between the two gonads. Serum LH was about 7 mU/l and FSH about 23 m

  4. The role of the 3' region of mammalian gonadotropin β subunit gene in the luteinizing hormone to chorionic gonadotropin evolution.

    PubMed

    Gabay, Reut; Rozen, Shelly; Samokovlisky, Albena; Amor, Yehudit; Rosenfeld, Rakefet; Kohen, Fortune; Amsterdam, Abraham; Berger, Peter; Ben-Menahem, David

    2014-02-15

    CGβ subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. It has evolved by incorporating a previously untranslated region of the LHβ gene into the reading frame. Although CTP-like sequences are encrypted in the LHβ genes of several mammals, the CGβ subunit developed only in primates and equids. To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LHβ gene (boCTP) possesses key characteristics of the human (h) CGβ-CTP. The boCTP does not impede several crucial aspects of hormone biosynthesis, but compared to the hCGβ-CTP, the stretch lacks O-glycans and determinants for circulatory survival. O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. This may explain why LH did not evolve into CG in ruminants and consequently alternative mechanisms evolved to delay luteolysis early in gestation.

  5. Advanced seasonal reproductive development in a male urban bird is reflected in earlier plasma luteinizing hormone rise but not energetic status.

    PubMed

    Davies, Scott; Behbahaninia, Hirbod; Giraudeau, Mathieu; Meddle, Simone L; Waites, Kyle; Deviche, Pierre

    2015-12-01

    Urban animals inhabit an environment considerably different than do their non-urban conspecifics, and to persist urban animals must adjust to these novel environments. The timing of seasonal reproductive development (i.e., growth of gonads and secondary sex organs) is a fundamental determinant of the breeding period and is frequently advanced in urban bird populations. However, the underlying mechanism(s) by which birds adjust the timing of reproductive development to urban areas remain(s) largely unknown. Here, we compared the timing of vernal reproductive development in free-ranging urban and non-urban male Abert's Towhees, Melozone aberti, in Phoenix, Arizona, USA, and tested the non-mutually exclusive hypotheses that earlier reproductive development is due to improved energetic status and/or earlier increase in endocrine activity of the reproductive system. We found that urban birds initiated testicular development earlier than non-urban birds, but this disparity was not associated with differences in body condition, fat stores, or innate immune performance. These results provide no support for the hypothesis that energetic constraints are responsible for delayed reproductive development of non-urban relative to urban male Abert's Towhees. Urban birds did, however, increase their plasma luteinizing hormone, but not plasma testosterone, earlier than non-urban birds. These findings suggest that adjustment to urban areas by Abert's Towhees involves increases in the endocrine activity of the anterior pituitary gland and/or hypothalamus earlier than non-urban towhees. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Expression of Vascular Endothelial Growth Factor A During Ligand-Induced Down-Regulation of Luteinizing Hormone Receptor in the Ovary☆

    PubMed Central

    Harada, M.; Peegel, H.; Menon, K. M. J.

    2010-01-01

    Vascular endothelial growth factor A (VEGF-A) is one of the most important regulators of ovarian angiogenesis. In this study, we examined the temporal relationship between VEGF-A and luteinizing hormone receptor (LHR) mRNA expression during ligand-induced down-regulation of LHR. Immature female rats were treated with pregnant mare’s serum gonadotropin followed by 25 IU hCG 56h later (day 0). On day 5, treatment with hCG (50 IU) to down-regulate LHR showed a temporal decrease in VEGF-A mRNA and protein levels in parallel with decreasing LHR mRNA. This effect was specific since the expression of CYP11A1 mRNA showed no decline. Examination of VEGF-A mRNA expression, using in situ hybridization histochemistry with 35S-labeled antisense VEGF-A mRNA probe, showed intense signal in the corpora lutea on day 5. Treatment with 50 IU hCG to down-regulate LHR mRNA showed a decline in the intensity of VEGF-A mRNA in the corpora lutea. VEGF-A mRNA expression returned to control level 53 hours later when the expression of LHR mRNA also recovered. These results show that the transient down-regulation of VEGF-A mRNA and protein closely parallels the ligand-induced down-regulation of LHR mRNA. The present study establishes a close association between VEGF-A and LHR mRNA expression, suggesting the possibility that VEGF-A-induced vascularization of the ovary is dictated by the expression of LHR and this might play a regulatory role in ovarian physiology. PMID:20619315

  7. Relationship among follicular growth, oestrus, time of ovulation, endogenous estradiol 17beta and luteinizing hormone in Bos indicus cows after a synchronization program.

    PubMed

    Maquivar, M; Verduzco, A; Galina, C S; Pulido, A; Rojas, S; Forster, K; Van der Laan, G; Arnoni, R

    2007-12-01

    To determine the pattern of follicular growth during oestrus and the relationship with estradiol and luteinizing hormone in ovulating and non-ovulating cows, three groups of (n = 10), thirty cyclic, Bos indicus cows were synchronized with CIDR, consecutively at 9-day intervals. Twenty-four hours after implant withdrawal, all cows synchronized in the same group with other cows displaying estrous behaviour after implant withdrawal were subjected to an intensive period of ultrasonographic observations (every 6 h for 120 h). Blood samples were taken to evaluate LH surge and 17-beta estradiol. No differences were observed in follicular growth, ovulatory diameter and growth average in the three groups of synchronized cows. Cows ovulating (CO) had a better growth average in comparison with the group of cows not ovulating (CNO) (1.4 +/- 0.7 mm vs 0.7 +/- 0.5 mm, p < 0.06). The average time from estradiol release to LH surge was 39.3 +/- 24.6 h. Differences were also observed between CO and CNO with respect to both the first concentration (27.7 +/- 5.2 vs 58.6 +/- 31.9, p < 0.004) and last concentration (79.3 +/- 23.3 vs 99.2 +/- 27.3, p < 0.05) of estradiol above 5 pg/ml. The average time from overt signs of oestrus to LH release was 8.4 +/- 7.7 h. In the CNO, the increase in LH concentration was never above two SD from the basal average. In conclusion, there is a wide variability in follicular growth and ovulatory diameter between CO and CNO, which can affect the intervals of LH release, estradiol peak and ovulation. Yet, LH surge might be a good marker for timing ovulation in Zebu cows.

  8. Effects of hypophysectomy and administration of pituitary hormones on luteal function and uptake of high density lipoproteins by luteinized ovaries and adrenals of the rat

    SciTech Connect

    Murphy, B.D.; Rajkumar, K.; McKibbin, P.E.; Macdonald, G.J.; Buhr, M.M.; Grinwich, D.L.

    1985-04-01

    The role of plasma lipoproteins and hypophyseal hormones in the maintenance of progesterone secretion by the rat corpus luteum was investigated. In the first experiment, rats were treated daily from days 1-6 of pregnancy with 5 mg/kg 4-aminopyrozolopyramidine (4APP), a blocker of hepatic lipoprotein secretion, or with 5 mg/kg 4APP and 1 or 2 mg ovine PRL or 0.1 ml 0.5% phosphoric acid (4APP vehicle). The administration of 4APP reduced serum cholesterol and progesterone levels on days 2-6 of pregnancy and ovarian progesterone on day 6. The reduced progesterone secretion had no effect on embryo implantation. PRL, in the doses used, was incapable of abrogating the effects of 4APP on circulating or ovarian progesterone levels. Ovaries and adrenals, but not kidneys, of pseudopregnant rats exhibited specific and saturable uptake of porcine high density lipoprotein (HDL). Time-course studies indicated that the uptake of HDL was rapid in ovaries compared to that in adrenals. Ovaries from rats not only exhibited uptake of porcine HDL, but also were capable of using it for progesterone synthesis. Treatment with 4APP increased the adrenal uptake of HDL, but ovarian uptake was not different from that in the control group. Hypophysectomy reduced both adrenal and ovarian uptake of HDL. In adrenals only ACTH at the dose employed ameliorated reduction of HDL uptake induced by hypophysectomy, while in the ovaries, both PRL and LH reversed the effect of hypophysectomy. The effect of PRL on uptake was specific to (/sup 125/I)HDL and did not alter (/sup 125/I)albumin uptake. It is concluded that: 1) hypophysectomy reduces HDL uptake in the luteinized rat ovary; and 2) PRL and LH replacement therapy maintain ovarian uptake of HDL, suggesting a direct effect of these luteotropins on lipoprotein uptake.

  9. The expression of CXCR4 is induced by the luteinizing hormone surge and mediated by progesterone receptors in human preovulatory granulosa cells.

    PubMed

    Choi, Yohan; Park, Ji Yeon; Wilson, Kalin; Rosewell, Katherine L; Brännström, Mats; Akin, James W; Curry, Thomas E; Jo, Misung

    2017-06-01

    The chemokine CXC motif ligand 12 (CXCL12) and its cognate receptor, CXCR4, have been implicated in the ovulatory process in various animal models. However, little is known about the expression and regulation of CXCL12 and CXCR4 and their functions during the ovulatory period in the human ovary. In this study, we characterized the expression patterns of CXCL12 and CXCR4 in preovulatory follicles collected before the luteinizing hormone (LH) surge and at defined hours after hCG administration in women with the regular menstrual cycle. The levels of mRNA and protein for CXCR4 were increased in granulosa cells of late ovulatory follicles, whereas CXCL12 expression was constant in follicles throughout the ovulatory period. Both CXCR4 and CXCL12 were localized to a subset of leukocytes around and inside the vasculature of human preovulatory follicles. Using a human granulosa cell culture model, the regulatory mechanisms and functions of CXCL12 and CXCR4 expression were investigated. Human chorionic gonadotropin (hCG) stimulated CXCR4 expression, whereas CXCL12 expression was not affected, mimicking in vivo expression patterns. Both RU486 (progesterone receptor antagonist) and CoCl2 (HIFs activator) blocked the hCG-induced increase in CXCR4 expression, whereas AG1478 (EGFR inhibitor) had no effect. The treatment with CXCL12 had no effect on granulosa cell viability but decreased hCG-stimulated CXCR4 expression. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Novel C617Y mutation in the 7th transmembrane segment of luteinizing hormone/choriogonadotropin receptor in a Japanese boy with peripheral precocious puberty.

    PubMed

    Nagasaki, Keisuke; Katsumata, Noriyuki; Ogawa, Yohei; Kikuchi, Toru; Uchiyama, Makoto

    2010-01-01

    Testotoxicosis, also known as familial male-limited precocious puberty, is an autosomal dominant form of gonadotropin-independent precocious puberty caused by heterozygous constitutively activating mutations of the LHCGR gene encoding the luteinizing hormone/choriogonadotropin receptor (LH/CGR). The patient is an 8-year-old boy who started to develop pubic hair and penile enlargement at 6 years of age. The patient had elevated serum testosterone levels, but initially exhibited a prepubertal response of gonadotropins to GnRH, which was followed by central activation of the hypothalamo-pituitary-gonadal axis. The father reported having experienced precocious puberty, and is 158 cm tall. There is no history of short stature and precocious puberty in the family except for the father. The LHCGR gene was analyzed by direct DNA sequencing of amplified PCR products from the patient and his parents. The wild-type and mutant LH/CGRs were transiently expressed in COS-1 cells and cAMP levels in the cells were determined with or without hCG stimulation. Genetic analysis revealed a novel C617Y mutation of the LHCGR gene in the patient and his mother, while his father had no mutations. Functional expression study demonstrated around 15% increase in the basal intracellular cAMP level in cells expressing the mutant LH/CGR compared with that in cells expressing the wild-type receptor. We have reported the first missense C617Y mutation located in the 7th transmembrane segment of LH/CGR causing testotoxicosis. The modest phenotype of our patient may be explained, at least in part, by the modest increase in the intracellular cAMP level caused by the C617Y mutation.

  11. Dephosphorylation of juxtamembrane serines and threonines of the NPR2 guanylyl cyclase is required for rapid resumption of oocyte meiosis in response to luteinizing hormone.

    PubMed

    Shuhaibar, Leia C; Egbert, Jeremy R; Edmund, Aaron B; Uliasz, Tracy F; Dickey, Deborah M; Yee, Siu-Pok; Potter, Lincoln R; Jaffe, Laurinda A

    2016-01-01

    The meiotic cell cycle of mammalian oocytes starts during embryogenesis and then pauses until luteinizing hormone (LH) acts on the granulosa cells of the follicle surrounding the oocyte to restart the cell cycle. An essential event in this process is a decrease in cyclic GMP in the granulosa cells, and part of the cGMP decrease results from dephosphorylation and inactivation of the natriuretic peptide receptor 2 (NPR2) guanylyl cyclase, also known as guanylyl cyclase B. However, it is unknown whether NPR2 dephosphorylation is essential for LH-induced meiotic resumption. Here, we prevented NPR2 dephosphorylation by generating a mouse line in which the seven regulatory serines and threonines of NPR2 were changed to the phosphomimetic amino acid glutamate (Npr2-7E). Npr2-7E/7E follicles failed to show a decrease in enzyme activity in response to LH, and the cGMP decrease was attenuated; correspondingly, LH-induced meiotic resumption was delayed. Meiotic resumption in response to EGF receptor activation was likewise delayed, indicating that NPR2 dephosphorylation is a component of the pathway by which EGF receptor activation mediates LH signaling. We also found that most of the NPR2 protein in the follicle was present in the mural granulosa cells. These findings indicate that NPR2 dephosphorylation in the mural granulosa cells is essential for the normal progression of meiosis in response to LH and EGF receptor activation. In addition, these studies provide the first demonstration that a change in phosphorylation of a transmembrane guanylyl cyclase regulates a physiological process, a mechanism that may also control other developmental events.

  12. Dephosphorylation of juxtamembrane serines and threonines of the NPR2 guanylyl cyclase is required for rapid resumption of oocyte meiosis in response to luteinizing hormone

    PubMed Central

    Shuhaibar, Leia C.; Egbert, Jeremy R.; Edmund, Aaron B.; Uliasz, Tracy F.; Dickey, Deborah M.; Yee, Siu-Pok; Potter, Lincoln R.; Jaffe, Laurinda A.

    2016-01-01

    The meiotic cell cycle of mammalian oocytes starts during embryogenesis and then pauses until luteinizing hormone (LH) acts on the granulosa cells of the follicle surrounding the oocyte to restart the cell cycle. An essential event in this process is a decrease in cyclic GMP in the granulosa cells, and part of the cGMP decrease results from dephosphorylation and inactivation of the natriuretic peptide receptor 2 (NPR2) guanylyl cyclase, also known as guanylyl cyclase B. However, it is unknown whether NPR2 dephosphorylation is essential for LH-induced meiotic resumption. Here, we prevented NPR2 dephosphorylation by generating a mouse line in which the seven regulatory serines and threonines of NPR2 were changed to the phosphomimetic amino acid glutamate (Npr2–7E). Npr2–7E/7E follicles failed to show a decrease in enzyme activity in response to LH, and the cGMP decrease was attenuated; correspondingly, LH-induced meiotic resumption was delayed. Meiotic resumption in response to EGF receptor activation was likewise delayed, indicating that NPR2 dephosphorylation is a component of the pathway by which EGF receptor activation mediates LH signaling. We also found that most of the NPR2 protein in the follicle was present in the mural granulosa cells. These findings indicate that NPR2 dephosphorylation in the mural granulosa cells is essential for the normal progression of meiosis in response to LH and EGF receptor activation. In addition, these studies provide the first demonstration that a change in phosphorylation of a transmembrane guanylyl cyclase regulates a physiological process, a mechanism that may also control other developmental events. PMID:26522847

  13. Activation of protein kinase Czeta mediates luteinizing hormone- or forskolin-induced NGFI-B expression in preovulatory granulosa cells of rat ovary.

    PubMed

    Park, Jae-Il; Kim, Sun-Gyun; Chun, Jang-Soo; Seo, You-Mi; Jeon, Mi-Jin; Ohba, Motoi; Kim, Hyun-Jin; Chun, Sang-Young

    2007-05-30

    We have previously demonstrated that luteinizing hormone (LH) induces a rapid and transient expression of NGFI-B in the ovary. In this report, we investigated the signaling pathway for LH- and forskolin-induced NGFI-B expression in cultured rat granulosa cells of preovulatory follicles. LH- or forskolin-induced NGFI-B expression was suppressed by high dose of protein kinase C (PKC) inhibitor RO 31-8220 (10 microM), but not by low doses RO 31-8220 (0.1-1.0 microM) or adenylate cyclase inhibitor MDL-12,300A, implicating the involvement of atypical PKCs. Kinase assay revealed that LH treatment of granulosa cells resulted in a rapid stimulation of atypical PKCzeta activity. Interestingly, like LH, forskolin was also able to activate PKCzeta. Treatment with the cell-permeable PKCzeta-specific inhibitor pseudosubstrate peptide inhibited LH-or forskolin-induced NGFI-B expression, indicating the essential role of PKCzeta. Consistent with this promise, in granulosa cells depleted of diacylglycerol sensitive PKCs by prolonged treatment with tetradecanoylphobol-13-acetate, LH or forskolin could still induce NGFI-B expression, and RO 31-8220 or the PKCzeta pseudosubstrate peptide inhibited LH- or forskolin-induced NGFI-B expression. Furthermore, overexpression of dominant-negative PKCzeta in primary granulosa cells using a replication-defective adenovirus vector resulted in the suppression of LH- or forskolin-induced NGFI-B expression. Our findings demonstrate that PKCzeta, which is activated by LH or forskolin, contributes to the induction of NGFI-B in granulosa cells of preovulatory follicles.

  14. Pituitary content of luteinizing hormone reveals species differences in the reproductive synchrony between males and females in Australian flying-foxes (genus Pteropus).

    PubMed

    O'Brien, G M; McFarlane, J R; Kearney, P J

    2003-01-01

    Flying-foxes (genus suborder, Pteropus Megachiroptera) are long-lived tropical mammals. Their seasonal reproduction appears to be regulated by an endogenous, circannual rhythm modified by multiple environmental cues. Luteinizing hormone (LH) content in pituitary extracts was examined to establish the broad time-frame of pituitary stages in the reproductive seasonality of the flying-foxes. A comparison was made between the grey-headed flying-fox P. poliocephalus, which mates and conceives in autumn, and the little red flying-fox P. scapulatus, which mates and conceives in spring. In P. scapulatus, LH was maximum during the spring mating season at 1494 ng mg(-1) in males and 896 ng mg(-1) in females. In P. poliocephalus males, LH increased to 1082 ng mg(-1) in early summer, 4 months before the mating season; LH concentrations in male P. poliocephalus returned to a low of 222 ng mg(-1) by the time of the autumn mating, by which time the female P. poliocephalus expressed elevated LH concentrations (624 ng mg(-1)). Apparently in P. poliocephalus, the peak LH concentrations in females are delayed by 4 months relative to LH concentrations in males. This is associated with 4 months of energetic courtship on the part of male P. poliocephalus, which is not observed in P. scapulatus, the fertility of which is synchronized between the sexes. The heterologous radioimmunoassay developed using monoclonal antibody 518B7 confirmed classic suppression of LH during pregnancy and lactation in flying-foxes and LH elevation in response to gonadectomy. Juveniles generally had pituitary levels similar to non-breeding levels in adults.

  15. Effect of investigational kisspeptin/metastin analog, TAK-683, on luteinizing hormone secretion at different stages of the luteal phase in goats.

    PubMed

    Rahayu, Larasati Puji; El Behiry, Mohammed; Endo, Natsumi; Tanaka, Tomomi

    2017-03-25

    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.

  16. The role of nutrition in the regulation of luteinizing hormone secretion by the opioidergic, dopaminergic, and serotonergic systems in female Mediterranean goats.

    PubMed

    Zarazaga, Luis A; Celi, Irma; Guzmán, José Luis; Malpaux, Benoît

    2011-03-01

    This study examined which neural mechanism (opioid, dopaminergic, or serotonergic system) is involved in the regulation of luteinizing hormone (LH) secretion, with and without nutritional modulation, at different times of the photoperiodic cycle. Goats were randomly distributed into two experimental groups that received either 1.1 (high group; n = 18) or 0.7 (low group; n = 18) times the nutritional maintenance requirements. The goats were exposed to alternations of 3 mo of long days and 3 mo of short days. Plasma LH concentrations were measured twice a week. The effects of intravenous injections of naloxone (endogenous opioid receptor antagonist), pimozide (dopaminergic(2) receptor antagonist), and cyproheptadine (serotonin 5-hydroxytryptamine(2) receptor antagonist) on LH secretion were assessed during challenges in three different photoperiodic situations: the onset of LH stimulation by short days (OnsetSD), the onset of LH inhibition by long days (OnsetLD), and during the LH inhibition by long days (LateLD). The role of the different neural systems was clearly modified by the level of nutrition. In the low-nutrition group, only naloxone increased LH concentrations during onsetLD (P < 0.05). However, in the high-nutrition group, naloxone increased the concentration and pulsatility of LH (P < 0.05) in onsetSD and onsetLD. Pimozide increased LH concentration and pulsatility (P < 0.05) in onsetLD and LH concentration in lateLD (P < 0.001). Finally, cyproheptadine significantly increased LH concentration at all three times (P < 0.001). These results provide evidence that all three systems are involved in the inhibition of LH release in onsetLD, and that the opioid and serotonin mechanisms are involved during the onsetSD that were enhanced by a high plane of nutrition.

  17. Effects of prenatal treatment with antiandrogens on luteinizing hormone secretion and sex steroid concentrations in adult spotted hyenas, Crocuta crocuta.

    PubMed

    Place, Ned J; Holekamp, Kay E; Sisk, Cheryl L; Weldele, Mary L; Coscia, Elizabeth M; Drea, Christine M; Glickman, Stephen E

    2002-11-01

    Prenatal androgen treatment can alter LH secretion in female offspring, often with adverse effects on ovulatory function. However, female spotted hyenas (Crocuta crocuta), renowned for their highly masculinized genitalia, are naturally exposed to high androgen levels in utero. To determine whether LH secretion in spotted hyenas is affected by prenatal androgens, we treated pregnant hyenas with antiandrogens (flutamide and finasteride). Later, adult offspring of the antiandrogen-treated (AA) mothers underwent a GnRH challenge to identify sex differences in the LH response and to assess the effects of prenatal antiandrogen treatment. We further considered the effects of blocking prenatal androgens on plasma sex steroid concentrations. To account for potential differences in the reproductive state of females, we suppressed endogenous hormone levels with a long-acting GnRH agonist (GnRHa) and then measured plasma androgens after an hCG challenge. Plasma concentrations of LH were sexually dimorphic in spotted hyenas, with females displaying higher levels than males. Prenatal antiandrogen treatment also significantly altered the LH response to GnRH. Plasma estradiol concentration was higher in AA-females, whereas testosterone and androstenedione levels tended to be lower. This trend toward lower androgen levels disappeared after GnRHa suppression and hCG challenge. In males, prenatal antiandrogen treatment had long-lasting effects on circulating androgens: AA-males had lower T levels than control males. The sex differences and effects of prenatal antiandrogens on LH secretion suggest that the anterior pituitary gland of the female spotted hyena is partially masculinized by the high androgen levels that normally occur during development, without adverse effects on ovulatory function.

  18. The effect of the intracervical application of follicle-stimulating hormone or luteinizing hormone on the pattern of expression of gonadotrophin receptors in the cervix of non-pregnant ewes.

    PubMed

    Leethongdee, S; Khalid, M; Scaramuzzi, R J

    2014-08-01

    During the periovulatory period, the cervix relaxes in response to changes in circulating concentrations of reproductive hormones. The present study investigated the role of gonadotrophins in cervical function by examining the expression of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) and their mRNAs following intracervical treatment with either FSH or LH. Eighteen ewes were assigned to four groups, and they were then treated with progestagen sponges and PMSG to synchronize their oestrous cycles. Intracervical treatments were given 24 h after sponge removal as follows: Group 1: FSH 2 mg; Group 2: LH 2 mg; Group 3: Vehicle and Group 4: Control. Cervices were collected 54 h after sponge removal and then divided into three regions. The expression of FSHR and LHR was determined by immunohistochemistry and FSHR mRNA and LH mRNA by in situ hybridization. The expression of LHR, FSHR and their respective mRNAs was compared in six tissue layers (luminal epithelium, subepithelial stroma, circular, longitudinal and transverse muscle and serosa) and in three cervical regions (vaginal, mid and uterine). The results showed that FSH increased transcription of the FSHR gene and the levels of its receptor, but only in subepithelial stroma of the cervix. FSH also increased the levels of LHR in the cervix, but only in the muscle layers. LH had no effect on the levels of FSHR despite the fact that it did increase the level of transcription of the FSHR gene and LH also increased the levels of its own receptor in the cervix, but only in the muscle layers, and this action was independent of increased levels of transcription of the LHR gene. These findings suggest multiple levels of regulation of cervical LH and FSH receptors and that the gonadotrophins may have a role in relaxation of the cervix during oestrus by regulating their own receptors.

  19. Chronic hypersecretion of luteinizing hormone in transgenic mice disrupts both ovarian and pituitary function, with some effects modified by the genetic background.

    PubMed

    Nilson, J H; Abbud, R A; Keri, R A; Quirk, C C

    2000-01-01

    When the pituitary or hypothalamus becomes resistant to steroid negative feedback, a vicious cycle ensues, resulting in chronic hypersecretion of luteinizing hormone (LH) from the pituitary and steroids from the ovaries. In women, LH hypersecretion is implicated in infertility, miscarriages, and development of granulosa cell tumors. Progress in defining the underlying mechanisms of LH toxicity, however, has been limited by the lack of well-defined animal models. To that end, we have developed a new transgenic mouse model (alpha-LHbetaCTP) wherein LH hypersecretion occurs chronically and results in several dire pathological outcomes. Chronic hypersecretion of LH was achieved by introducing a transgene containing a bovine alpha subunit promoter fused to the coding region of a chimeric LHbeta subunit. The alpha subunit promoter directs transgene expression only to gonadotropes. The LHbeta chimera contains the carboxyl-terminal peptide (CTP) of the human chorionic gonadotropin beta subunit linked to the carboxyl terminus of bovine LHbeta. This carboxyl extension extends the half-life of LH heterodimers that contain the chimeric beta subunit. In intact alpha-LHbetaCTP females, serum LH is elevated five- to ten-fold in comparison to nontransgenic littermates. Levels of testosterone (T) and estradiol (E2) also are elevated, with an overall increase in the T-to-E2 ratio. These transgenic females enter puberty precociously but are anovulatory and display a prolonged luteal phase. Anovulation reflects the absence of gonadotropin-releasing hormone (GnRH) and the inability to produce a pre-ovulatory surge of LH. The ovaries are enlarged, with reduced numbers of primordial follicles and numerous, giant, hemorrhagic follicles. Despite the pathological appearance of the ovary, females can be superovulated and mated. Although pregnancy occurs, implantation is compromised due to defects in uterine receptivity. In addition, pregnancy fails at midgestation, reflecting a maternal

  20. Endotoxin disrupts the estradiol-induced luteinizing hormone surge: interference with estradiol signal reading, not surge release.

    PubMed

    Battaglia, D F; Beaver, A B; Harris, T G; Tanhehco, E; Viguié, C; Karsch, F J

    1999-06-01

    delivery and surge onset), nor does it prevent actual hormonal surge output. Thus, endotoxin appears to disrupt estrogen action per se rather than the release of GnRH or LH at the time of the surge.

  1. Molecular cloning and characterization of pirarucu (Arapaima gigas) follicle-stimulating hormone and luteinizing hormone β-subunit cDNAs

    PubMed Central

    Sevilhano, Thais; de Carvalho, Roberto Feitosa; Oliveira, Nélio Alessandro de Jesus; Oliveira, João Ezequiel; Maltarollo, Vinicius Gonçalves; Trossini, Gustavo; Garcez, Riviane; Bartolini, Paolo

    2017-01-01

    The common gonadotrophic hormone α-subunit (GTHα) has been previously isolated by our research group from A. gigas pituitaries; in the present work the cDNA sequences encoding FSHβ and LHβ subunits have also been isolated from the same species of fish. The FSH β-subunit consists of 126 amino acids with a putative 18 amino acid signal peptide and a 108 amino acid mature peptide, while the LH β-subunit consists of 141 amino acids with a putative 24 amino acid amino acid signal peptide and a 117 amino acid mature peptide. The highest identity, based on the amino acid sequences, was found with the order of Anguilliformes (61%) for FSHβ and of Cypriniformes (76%) for LHβ, followed by Siluriformes, 53% for FSHβ and 75% for LHβ. Interestingly, the identity with the corresponding human amino acid sequences was still remarkable: 45.1% for FSHβ and 51.4% for LHβ. Three dimensional models of ag-FSH and ag-LH, generated by using the crystal structures of h-FSH and h-LH as the respective templates and carried out via comparative modeling and molecular dynamics simulations, suggested the presence of the so-called “seat-belt”, favored by a disulfide bond formed between the 3rd and 12th cysteine in both β-subunits. The sequences found will be used for the biotechnological synthesis of A. gigas gonadotrophic hormones (ag-FSH and ag-LH). In a first approach, to ascertain that the cloned transcripts allow the expression of the heterodimeric hormones, ag-FSH has been synthesized in human embryonic kidney 293 (HEK293) cells, preliminarily purified and characterized. PMID:28846736

  2. Serum copper, follicular stimulating hormone, luteinizing hormone, prolactin, spermatic count, viability, progression and seminal zinc correlations in a human (male) infertility study

    SciTech Connect

    Sella, G.E.; Cunnane, S.C.; McInnes, R.A.

    1981-06-01

    The role of copper and its correlations to other parameters has been investigated in a male-fertility pilot study at a University infertility clinic in Montreal. Serum and semen Cu concentrations were determined in 100 men (age 25 to 54 years) referred to the clinic for infertility evaluation. The results of the significant correlations between serum Cu concentrations and male fertility parameters such as (1) the serum concentrations of the hormones FSH, LH and prolactin; (2) spermatozoal count, viability and progression and (3) seminal zinc concentrations are reported.

  3. Associations of total testosterone, sex hormone-binding globulin, calculated free testosterone, and luteinizing hormone with prevalence of abdominal aortic aneurysm in older men.

    PubMed

    Yeap, Bu B; Hyde, Zoë; Norman, Paul E; Chubb, S A Paul; Golledge, Jonathan

    2010-03-01

    Abdominal aortic aneurysm (AAA) is associated with mortality in older adults, and increasing aortic diameter predicts incident cardiovascular events. Although AAA occurs predominantly in men, its association with male sex hormones is unclear. The objective of the study was to examine whether male sex hormones are independently associated with AAA or increased abdominal aortic diameter. This was a cross-sectional analysis. Participants included 3620 community-dwelling men aged 70-88 yr. Abdominal aortic diameter was measured with ultrasound. Early morning sera were assayed for total testosterone, SHBG, and LH. Free testosterone was calculated using mass action equations. AAA (aortic diameter > or =30 mm) was present in 262 men (7.2%). Men with AAA had lower serum total and free testosterone (mean +/- sd 14.5 +/- 6.0 vs. 15.5 +/- 5.6 nmol/liter, P = 0.005 and 256 +/- 87 vs. 280 +/- 97 pmol/liter, P < 0.001, respectively) compared with men without. LH was higher in men with AAA (median, interquartile range: 4.9, 3.1-7.9 vs. 4.3, 3.0-6.4 IU/liter, P = 0.013). In multivariate analysis adjusting for potential confounders, free testosterone was negatively associated with AAA (odds ratio per 1 sd increase: 0.84, 95% confidence interval 0.72-0.98, P = 0.026). LH was positively associated (odds ratio 1.14, 95% confidence interval 1.03-1.25, P = 0.008). Comparable results were seen with aortic diameter analyzed as a continuous variable. Lower free testosterone and higher LH levels are independently associated with AAA in older men. Impaired gonadal function may be involved in arterial dilatation as well as occlusive vascular disease in older men. Additional studies are needed to clarify direction of causality and determine possible scope for preventive intervention.

  4. Dihydropyridine-sensitive calcium channel activity related to prolactin, growth hormone, and luteinizing hormone release from anterior pituitary cells in culture: interactions with somatostatin, dopamine, and estrogens

    SciTech Connect

    Drouva, S.V.; Rerat, E.; Bihoreau, C.; Laplante, E.; Rasolonjanahary, R.; Clauser, H.; Kordon, C.

    1988-12-01

    In the present work, we determined the activity of voltage-dependent dihydropyridine (DHP)-sensitive Ca2+ channels related to PRL, GH, and LH secretion in primary cultures of pituitary cells from male or female rats. We investigated their modulation by 17 beta-estradiol (E2) and their involvement in dopamine (DA) and somatostatin (SRIF) inhibition of PRL and GH release. BAY-K-8644 (BAYK), a DHP agonist which increases the opening time of already activated channels, stimulated PRL and GH secretion in a dose-dependent manner. The effect was more pronounced on PRL than on GH release. BAYK-evoked hormone secretion was further amplified by simultaneous application of K+ (30 or 56 mM) to the cell cultures; in parallel, BAYK-induced 45Ca uptake by the cells was potentiated in the presence of depolarizing stimuli. In contrast, BAYK was unable to stimulate LH secretion from male pituitary cells, but it potentiated LHRH- as well as K+-induced LH release; it had only a weak effect on LH secretion from female cell cultures. Basal and BAYK-induced pituitary hormone release were blocked by the Ca2+ channel antagonist nitrendipine. Under no condition did BAYK affect the hydrolysis of phosphoinositides or cAMP formation. Pretreatment of female pituitary cell cultures with E2 (10(-9) M) for 72 h enhanced LH and PRL responses to BAYK, but was ineffective on GH secretion. DA (10(-7) M) inhibited basal and BAYK-induced PRL release from male or female pituitary cells treated or not treated with E2 (10(-9) M). SRIF (10(-9) and 10(-8) M) reversed BAYK-evoked GH release to the same extent in cell cultures derived from male or female animals. It was ineffective on BAYK-induced PRL secretion in the absence of E2, but antagonized it after E2 pretreatment. The effect was dependent upon the time of steroid treatment and was specific, since 17 alpha-estradiol was inactive.

  5. Effects of long-term treatment with the luteinizing hormone-releasing hormone (LHRH) agonist Decapeptyl and the LHRH antagonist Cetrorelix on the levels of pituitary LHRH receptors and their mRNA expression in rats

    PubMed Central

    Horvath, Judit E.; Bajo, Ana M.; Schally, Andrew V.; Kovacs, Magdolna; Herbert, Francine; Groot, Kate

    2002-01-01

    The effects of depot formulations of the luteinizing hormone-releasing hormone (LHRH) agonist Decapeptyl (25 μg/day) for 30 days or LHRH antagonist Cetrorelix pamoate (100 μg/day) for 30 days and daily injections of 100 μg of Decapeptyl for 10 days on the expression of mRNA for pituitary LHRH receptor (LHRH-R) and the levels of LHRH-R protein were evaluated in rats. Serum sex steroid concentrations and the weights of the reproductive organs were greatly reduced in all groups treated with analogs, demonstrating an efficient blockade of the pituitary–gonadal axis. Decapeptyl microcapsules elevated serum LH in female rats, but decreased it in male rats. LHRH-R mRNA expression in female pituitaries was reduced to 41% and 56–65% on days 10 and 30, respectively, whereas LHRH-R protein was 64% of control on day 10 and returned to pretreatment levels on day 30. Decapeptyl microcapsules reduced LHRH-R mRNA expression in male pituitaries to 58% on day 30 but not LHRH-R protein. Daily injections of Decapeptyl caused a desensitization of LH responses in female rats, while raising LHRH-R mRNA expression in female rats by 23% and LHRH-R protein levels by 119%. Cetrorelix pamoate reduced serum LH in female rats and diminished LHRH-R mRNA to 30% and 26% and LHRH-R protein to 57% and 48% on days 10 and 30, respectively. Elevated LHRH-R protein levels of ovariectomized rats were reduced after 10-day treatment with Cetrorelix or 100 μg/day Decapeptyl. Thus, changes in the mRNA expression after treatment with Cetrorelix, but not always Decapeptyl, paralleled those of LHRH-R protein. The inhibitory effect of Cetrorelix on serum LH, pituitary LHRH-R mRNA, and LHRH-R protein was greater than that of Decapeptyl. PMID:12409615

  6. Neoadjuvant luteinizing-hormone-releasing hormone agonist plus low-dose estramustine phosphate improves prostate-specific antigen-free survival in high-risk prostate cancer patients: a propensity score-matched analysis.

    PubMed

    Koie, Takuya; Mitsuzuka, Koji; Yoneyama, Takahiro; Narita, Shintaro; Kawamura, Sadafumi; Kaiho, Yasuhiro; Tsuchiya, Norihiko; Tochigi, Tatsuo; Habuchi, Tomonori; Arai, Yoichi; Ohyama, Chikara; Yoneyama, Tohru; Tobisawa, Yuki

    2015-10-01

    The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) in high-risk Pca patients treated with a neoadjuvant therapy comprising a luteinizing-hormone-releasing hormone (LHRH) agonist plus low dose estramustine phosphate (EMP) (LHRH+EMP) followed by radical prostatectomy (RP). In the present study, we used a retrospective design via propensity score matching to elucidate the clinical benefit of neoadjuvant LHRH+EMP for high-risk Pca. The Michinoku Urological Cancer Study Group database contained data for 1,268 consecutive Pca patients treated with RP alone at 4 institutions between April 2000 and March 2011 (RP alone group). In the RP alone group, we identified 386 high-risk Pca patients. The neoadjuvant LHRH+EMP group included 274 patients with high-risk Pca treated between September 2005 and November 2013 at Hirosaki University. Neoadjuvant LHRH+EMP therapy included LHRH and EMP administration at a dose of 280 mg/day for 6 months before RP. The outcome measures were overall survival (OS) and BRFS. The propensity score-matched analysis indicated 210 matched pairs from both groups. The 5-year BRFS rates were 90.4 and 65.8 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P < 0.0001). The 5-year OS rates were 100 and 96.1 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P = 0.110). Although the present study was not randomized, neoadjuvant LHRH+EMP therapy followed by RP appeared to reduce the risk of biochemical recurrence. A prospective randomized study is warranted to determine the clinical implications of the neoadjuvant therapy described here.

  7. Mechanisms for luteinizing hormone induction of growth hormone gene transcription in fish model: crosstalk of the cAMP/PKA pathway with MAPK-and PI3K-dependent cascades.

    PubMed

    Sun, Caiyun; He, Mulan; Ko, Wendy K W; Wong, Anderson O L

    2014-02-15

    In our previous studies in grass carp pituitary cells, local production of luteinizing hormone (LH) was shown to induce growth hormone (GH) production and gene expression, which constitutes a major component of the "intrapituitary feedback loop" regulating GH secretion and synthesis via autocrine/paracrine interactions between gonadotrophs and somatotrophs in the carp pituitary. To further investigate the signaling mechanisms mediating LH action at the transcriptional level, promoter studies were performed in GH3 cells co-transfected with the expression vector for carp LH receptor and luciferase-expressing reporter constructs with grass carp GH promoter. In this cell model, treatment with human chorionic gonadotropin (hCG) was effective in increasing GH promoter activity and the responsive sequence was mapped to position -616 and -572 of the grass carp GH promoter. GH promoter activation induced by hCG occurred with concurrent rise in cAMP production, CREB phosphorylation, and could be inhibited by inactivation of adenylate cyclase (AC), PKA, MEK1/2, P(38) MAPK, PI3K and mTOR. AC activation, presumably via cAMP production, could mimic hCG-induced CREB phosphorylation and GH promoter activity, and these stimulatory effects were also sensitive to the blockade of PKA-, MAPK- and PI3K- dependent cascades. These results, as a whole, suggest that LH receptor activation in the carp pituitary may trigger GH gene transcription through CREB phosphorylation as a result of the functional crosstalk of the cAMP/PKA pathway with MAPK-and PI3K-dependent cascades.

  8. Effect of testosterone and bovine follicular fluid on concentrations of luteinizing hormone and follicle-stimulating hormone in plasma of castrated rams that are homozygous carriers or non-carriers of the Booroola fecundity gene.

    PubMed

    Price, C A; Hudson, N L; McNatty, K P

    1992-08-01

    Castrated adult FecBFecB and Fec+Fec+ Booroola rams were injected with charcoal-treated bovine follicular fluid (bFF) (a source of inhibin-like activity) or given testosterone implants to examine whether the fecundity gene (FecB) influences sensitivity to negative feedback hormones in males. Mean concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) did not differ between genotypes before treatment. In Expt 1, injections of 5 ml bFF, but not of 1 ml (each given four times at intervals of 8 h), significantly (P < 0.05) depressed concentrations of LH and FSH, but there was no effect of genotype. After treatment, gonadotrophin concentrations returned to pretreatment values and for 2-2.5 days scaled (divided by pretreatment mean) LH values (235 +/- 49 for FecBFecB and 96 +/- 26% for Fec+Fec+ rams; P < 0.05) and scaled FSH values (106 +/- 5 for FecBFecB and 85 +/- 5% for Fec+Fec+ rams; P < 0.05) were significantly higher in FecBFecB than in Fec+Fec+ rams in the group that received 5 ml bFF. Irrespective of genotype, treatment with 5 ml bFF did not reduce mean FSH to concentrations observed in testis-intact rams. In Expt 2, Silastic envelopes were implanted subdermally to give physiological or supraphysiological circulating concentrations of testosterone. Both doses significantly reduced scaled LH values in a biphasic manner, such that there was an initial suppression followed by a short-lived increase. During the initial period of suppression in the lower dose group, mean scaled LH values were significantly higher in FecBFecB than in Fec+Fec+ rams (48.3 +/- 7.5 versus 23.1 +/- 5.5%; P < 0.05). Low doses of testosterone decreased LH pulse frequency in both genotypes but decreased (P < 0.05) pulse amplitude and mean concentrations in the Fec+Fec+ animals only. In nonimplanted control rams, mean LH concentrations (in samples taken every 10 min for 12 h) were significantly lower in FecBFecB than in Fec+Fec+ rams (0.6 +/- 0.2 versus 1.3 +/- 0.1 ng

  9. Relative messenger RNA abundance in bovine oocytes collected in vitro or in vivo before and 20 hr after the preovulatory luteinizing hormone surge.

    PubMed

    Lonergan, Patrick; Gutiérrez-Adán, Alfonso; Rizos, Dimitrios; Pintado, Belen; de la Fuente, Julio; Boland, Maurice P

    2003-11-01

    In the cyclic cow, final maturation of the ovulatory follicle is initiated by the preovulatory luteinizing hormone (LH) surge. During the subsequent 24 hr period, the oocyte nucleus undergoes meiotic progression to metaphase II and several changes in cytoplasmic organization take place. We have previously shown that oocytes recovered at the time of the LH peak and matured in vitro are less competent to reach the blastocyst stage than their counterparts recovered 20 hr later following in vivo maturation, despite both groups undergoing IVF and culture in parallel. The objective of this study was to compare, using real-time quantitative RT-PCR, the relative abundance of various developmentally important gene transcripts in these oocytes. The groups used were mature bovine oocytes originating from: (1) 2-6 mm follicles from slaughterhouse ovaries; (2) preovulatory follicles punctured by ovum pick-up just before the LH surge (i.e., immature) and matured in vitro; or (3) preovulatory follicles punctured 20 hr later, just prior to ovulation (i.e., in vivo matured). In addition, immature oocytes from 2-6 mm follicles were examined. We examined the relative mRNA expression of five enzymes involved in protection against free oxygen radicals (mitochondrial Mn-superoxide dismutase, MnSOD, cytosolic Cu/Zn superoxide dismutase, Cu/ZnSOD, gamma-glutamyl-cysteine transferase, GCS, glutathione peroxidase, GPX, sarcosine oxidase, SOX), a transcript involved in follicular development (growth differentiation factor-9, GDF-9), transcripts involved in glucose metabolism (glucose-6-phosphate dehydrogenase, G6PDH, glucose transporter type-1 and -8, Glut-1, Glut-8) and genes involved in cell cycle events, Cyclin A and B, and poly(A) polymerase (PAP). Transcripts for all genes were detected, irrespective of oocyte origin. While differences were not significant in all cases, variations in levels of transcript abundance between the groups were related to developmental competence. In

  10. Chronic estradiol-17β exposure suppresses hypothalamic norepinephrine release and the steroid-induced luteinizing hormone surge: Role of nitration of tyrosine hydroxylase

    PubMed Central

    Kasturi, Badrinarayanan S.; Mohan Kumar, Sheba M.J.; Sirivelu, Madhu P.; Shin, Andrew C.; Kumar, P.S. Mohan

    2012-01-01

    Chronic exposure to estrogens is known to produce a variety of deleterious effects in women including breast and ovarian cancer and anovulation. In female rats, exposure to low levels of estradiol-17β (E2) decreases hypothalamic norepinephrine (NE) to suppress luteinizing hormone (LH) secretion and cause failure of ovulation. We hypothesized that E2 exposure most likely decreases NE release in the medial preoptic area (MPA) of the hypothalamus to produce this effect and that this may be due to E2- induced inflammatory changes in noradrenergic nuclei leading to nitration of an enzyme involved in NE synthesis. To test this, female Sprague Dawley rats were sham implanted or implanted with slow release E2 pellets (20 ng/day) for 30, 60 or 90 days (E30, E60 and E90 respectively). At the end of the treatment period, the rats were implanted with a push-pull cannula in the MPA, ovariectomized and subjected to steroid priming to induce a LH surge. Perfusates were analyzed for NE levels using HPLC-EC. Blood samples collected simultaneously were analyzed for LH levels. We measured interleukin-1β (IL-1 β) and nitrate levels in brainstem noradrenergic nuclei that innervate the MPA. In control animals, there was a marked increase in NE levels in response to steroid priming at 1600h that was reduced in the E30 group, and completely abolished after 60 and 90 days of E2 exposure. LH profiles were similar to NE release profiles in control and E2-treated animals. We found that IL-1β levels increased in all three (A1, A2 and A6) noradrenergic nuclei with chronic E2 exposure, while nitrate levels increased only in the A6 region. There was an increase in the nitration of the NE synthesizing enzyme in the MPA in this group as well probably contributing to reduced NE synthesis. This could be a possible mechanism by which chronic E2 exposure decreases NE levels in the MPA to suppress the LH surge. PMID:23194835

  11. Unusual side effect from a luteinizing hormone-releasing hormone agonist, leuprorelin, in the treatment of prostate cancer: a case report.

    PubMed

    Chang, John I-Chiang; Bucci, Joseph

    2016-11-11

    The treatment options for high-risk prostate cancer are either radical prostatectomy or radiotherapy/brachytherapy depending on the patients' prognosis. In older men with multiple comorbidities, radiotherapy with androgen deprivation therapy is an attractive option. Common side effects of androgen deprivation therapy include hot flushes, tiredness, increased risk of fractures, increased risk of metabolic disorders, coronary heart disease, and psychological effects. This case highlights the potential side effect of lipodystrophy secondary to leuprolide acetate injections. To the best of our knowledge, this is the first reported case of such an instance. In this case report, we describe a 70-year-old white man with prostate-specific antigen of 1.8 ng/mL, clinical stage T2bN0M0, Gleason 4+5=9 prostate cancer who developed an unusual side effect from leuprolide acetate as part of his androgen deprivation therapy. Approximately 2 months after the initial 3-monthly injection of leuprolide acetate (Eligard 22.5 mg) our patient developed abnormal lipid deposition particularly in his deltoid and abdominal region. His upper limb mobility gradually became compromised due to the size of these abnormal fat depositions. He had liposuction to correct this lipodystrophy and had a good functional outcome and cosmesis from the procedure. To the best of our knowledge, this is the first reported case of lipodystrophy secondary to leuprolide acetate injections. Leuprolide acetate in commonly used as one of the gonadotrophin-releasing hormone agonists and thus we should be mindful of the potential effect of producing lipodystrophy, especially in patients with cirrhosis, and to watch for any signs and symptoms as appropriate. The implication of this potential side effect poses difficult management strategies for such patients, and second-line alternatives such as chemotherapy may need to be considered.

  12. Effects of immunization against luteinizing hormone-releasing hormone and treatment with trenbolone acetate on reproductive function of beef bulls and steers.

    PubMed

    Geary, T W; Wells, K J; deAvila, D M; deAvila, J; Conforti, V A; McLean, D J; Roberts, A J; Waterman, R W; Reeves, J J

    2011-07-01

    summary, LHRH immunization decreased synthesis and storage of LH and decreased storage, but not synthesis of FSH in bulls. The increased synthesis of LH and FSH in nonimmunized, but not LHRH-immunized steers suggests that castration removes the negative feedback on gonadotropin synthesis but that LHRH is still needed for release of these hormones. Androgen replacement with TBA did not restore the negative feedback control of gonadotropin synthesis.

  13. Recombinant human follicle-stimulating hormone (r-hFSH) plus recombinant luteinizing hormone versus r-hFSH alone for ovarian stimulation during assisted reproductive technology: systematic review and meta-analysis

    PubMed Central

    2014-01-01

    Background The potential benefit of adding recombinant human luteinizing hormone (r-hLH) to recombinant human follicle-stimulating hormone (r-hFSH) during ovarian stimulation is a subject of debate, although there is evidence that it may benefit certain subpopulations, e.g. poor responders. Methods A systematic review and a meta-analysis were performed. Three databases (MEDLINE, Embase and CENTRAL) were searched (from 1990 to 2011). Prospective, parallel-, comparative-group randomized controlled trials (RCTs) in women aged 18–45 years undergoing in vitro fertilization, intracytoplasmic sperm injection or both, treated with gonadotrophin-releasing hormone analogues and r-hFSH plus r-hLH or r-hFSH alone were included. The co-primary endpoints were number of oocytes retrieved and clinical pregnancy rate. Analyses were conducted for the overall population and for prospectively identified patient subgroups, including patients with poor ovarian response (POR). Results In total, 40 RCTs (6443 patients) were included in the analysis. Data on the number of oocytes retrieved were reported in 41 studies and imputed in two studies. Therefore, data were available from 43 studies (r-hFSH plus r-hLH, n = 3113; r-hFSH, n = 3228) in the intention-to-treat (ITT) population (all randomly allocated patients, including imputed data). Overall, no significant difference in the number of oocytes retrieved was found between the r-hFSH plus r-hLH and r-hFSH groups (weighted mean difference −0.03; 95% confidence interval [CI] −0.41 to 0.34). However, in poor responders, significantly more oocytes were retrieved with r-hFSH plus r-hLH versus r-hFSH alone (n = 1077; weighted mean difference +0.75 oocytes; 95% CI 0.14–1.36). Significantly higher clinical pregnancy rates were observed with r-hFSH plus r-hLH versus r-hFSH alone in the overall population analysed in this review (risk ratio [RR] 1.09; 95% CI 1.01–1.18) and in poor responders (n = 1179; RR 1.30; 95% CI 1

  14. Effect of a gonadotropin-releasing factor vaccine on follicle-stimulating hormone and luteinizing hormone concentrations and on the development of testicles and the expression of boar taint in male pigs.

    PubMed

    Fuchs, T; Thun, R; Parvizi, N; Nathues, H; Koehrmann, A; Andrews, S; Brock, F; Klein, G; Sudhaus, N; Grosse Beilage, E

    2009-09-15

    The objective of this study was to determine the effect of using a gonadotropin-releasing factor (GnRF) vaccine on follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations in plasma, the size of testicles, and the expression of boar taint in male pigs. Vaccinated pigs were compared with surgically castrated pigs and entire males. Pigs were randomly assigned to three treatment groups: surgically castrated during the first week of life (T01, n=274), immunized twice during the fattening period with a GnRF vaccine, the first when 13 to 14 wk of age and the second when 20 to 21 wk of age (T02, n=280), and entire males (T03, n=56). From a subgroup of both T01 and T02 and from all pigs of group T03, blood samples were collected immediately before second vaccination (T02) and again before slaughter at either 24 to 25 or 26 to 27 wk of life to determine the plasma concentrations of LH and FSH. Testicles were removed after slaughter and their size was determined. Meat and fat samples from all pigs of T02 and T03 as well as 25% of the pigs of T01 were examined with the cold cooking and fat melting test. Immediately before the second vaccination (T02 only), LH and FSH concentrations were not significantly different between T02 and T03. However, LH and FSH concentrations were significantly higher in T01 compared with T02 and T03. Before the first slaughter date, LH and FSH concentrations were significantly lower in T02 than in T03. Testicle size was significantly lower in T02 compared with that in T03. In T02, 98% (235 of 239) of the samples were rated negative for boar taint by the cooking test, whereas in T03, 94% (48 of 51) were rated positive. In the fat melting test, 97% of T02 were rated negative and 3% (7 pigs) were rated positive, including the pigs tested positive in the cold cooking test. In T03, 94% were rated positive. All pigs (7 of 239) in T02 that were positive for boar taint in the cooking or melting test and that were tested had

  15. Lutein and Brain Function

    PubMed Central

    Erdman, John W.; Smith, Joshua W.; Kuchan, Matthew J.; Mohn, Emily S.; Johnson, Elizabeth J.; Rubakhin, Stanislav S.; Wang, Lin; Sweedler, Jonathan V.; Neuringer, Martha

    2015-01-01

    Lutein is one of the most prevalent carotenoids in nature and in the human diet. Together with zeaxanthin, it is highly concentrated as macular pigment in the foveal retina of primates, attenuating blue light exposure, providing protection from photo-oxidation and enhancing visual performance. Recently, interest in lutein has expanded beyond the retina to its possible contributions to brain development and function. Only primates accumulate lutein within the brain, but little is known about its distribution or physiological role. Our team has begun to utilize the rhesus macaque (Macaca mulatta) model to study the uptake and bio-localization of lutein in the brain. Our overall goal has been to assess the association of lutein localization with brain function. In this review, we will first cover the evolution of the non-human primate model for lutein and brain studies, discuss prior association studies of lutein with retina and brain function, and review approaches that can be used to localize brain lutein. We also describe our approach to the biosynthesis of 13C-lutein, which will allow investigation of lutein flux, localization, metabolism and pharmacokinetics. Lastly, we describe potential future research opportunities. PMID:26566524

  16. Circannual changes in progesterone secretion in intact ewes, luteinizing hormone secretion in ovariectomized estradiol-implanted ewes, and prolactin secretion in three sheep breeds anticipated to differ in seasonality of reproduction.

    PubMed

    Goff, Katherine J; Knight, James W; Pelzer, Kevin D; Akers, R Michael; Notter, David R

    2013-05-01

    Changes in progesterone secretion in intact ewes (7 or 9 per breed) and luteinizing hormone secretion in ovariectomized, estradiol-implanted ewes (9 or 10 per breed) were monitored for 12 mo in Suffolk, tropically adapted St. Croix, and OOS ewes. The OOS line is a composite population of 50% Dorset, 25% Rambouillet, and 25% Finnish Landrace breeding that was selected for 10 yr for ability to lamb in October and early November. Ewes were isolated from rams, and blood samples were collected twice weekly. Circulating prolactin concentrations were also determined from blood samples collected near the summer and winter solstice and vernal and autumnal equinox. Intact OOS ewes entered anestrus later, began the subsequent breeding season sooner, and had a shorter seasonal anestrus than Suffolk and St. Croix ewes (P ≤ 0.005). St. Croix ewes did not differ from Suffolk ewes in date of onset or cessation of breeding or duration of anestrus (P ≥ 0.06). Breed differences in duration of luteinizing hormone inhibition in ovariectomized ewes were essentially identical to those observed for duration of anestrous. Prolactin concentrations varied during the year: annual changes were larger in relatively seasonal Suffolk ewes than in tropically-derived St. Croix ewes (P<0.01), and OOS ewes were intermediate to, and tended to differ from (P<0.10), the other two breeds. We conclude that OOS ewes developed by selection for fertility in spring matings had an abbreviated seasonal anestrus that is one of the shortest ever reported for temperate breeds, and that tropical St. Croix sheep did not have a shorter seasonal anestrus than Suffolk sheep under temperate conditions and ram isolation. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Insulin-like growth factor-1, insulin-like growth factor-binding protein-3, growth hormone, and mammographic density in the Nurses' Health Studies.

    PubMed

    Rice, Megan S; Tworoger, Shelley S; Rosner, Bernard A; Pollak, Michael N; Hankinson, Susan E; Tamimi, Rulla M

    2012-12-01

    Higher circulating insulin-like growth factor I (IGF-1) levels have been associated with higher mammographic density among women in some, but not all studies. Also, few studies have examined the association between mammographic density and circulating growth hormone (GH) in premenopausal women. We conducted a cross-sectional study among 783 premenopausal women and 436 postmenopausal women who were controls in breast cancer case-control studies nested in the Nurses' Health Study (NHS) and NHSII. Participants provided blood samples in 1989-1990 (NHS) or in 1996-1999 (NHSII), and mammograms were obtained near the time of blood draw. Generalized linear models were used to assess the associations of IGF-1, IGF-binding protein-3 (IGFBP-3), IGF-1:IGFBP-3 ratio, and GH with percent mammographic density, total dense area, and total non-dense area. Models were adjusted for potential confounders including age and body mass index (BMI), among others. We also assessed whether the associations varied by age or BMI. In both pre- and postmenopausal women, percent mammographic density was not associated with plasma levels of IGF-1, IGFBP-3, or the IGF-1:IGFBP-3 ratio. In addition, GH was not associated with percent density among premenopausal women in the NHSII. Similarly, total dense area and non-dense area were not significantly associated with any of these analytes. In postmenopausal women, IGF-1 was associated with higher percent mammographic density among women with BMI <25 kg/m(2), but not among overweight/obese women. Overall, plasma IGF-1, IGFBP-3, and GH levels were not associated with mammographic density in a sample of premenopausal and postmenopausal women.

  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

    PubMed Central

    Koo, Hwa Seon; Cha, Sun Hwa; Kim, Hye Ok; Song, In Ok; Min, Eung Gi; Yang, Kwang Moon

    2015-01-01

    Objective 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. Methods 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. Results 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. Conclusion Measuring serum P4 values at the time of hCG administration is necessary in order to determine the optimal strategy for embryo transfer. PMID:26816874

  19. A high response to controlled ovarian stimulation induces premature luteinization with a negative impact on pregnancy outcomes in a gonadotropin-releasing hormone antagonist cycle.

    PubMed

    Koo, Hwa Seon; Cha, Sun Hwa; Kim, Hye Ok; Song, In Ok; Min, Eung Gi; Yang, Kwang Moon; Park, Chan Woo

    2015-12-01

    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.

  20. Nitro-thiocyanobenzoic acid (NTCB) reactivity of cysteines beta100 and beta110 in porcine luteinizing hormone: metastability and hypothetical isomerization of the two disulfide bridges of its beta-subunit seatbelt.

    PubMed

    Belghazi, Maya; Klett, Danièle; Cahoreau, Claire; Combarnous, Yves

    2006-03-09

    Luteinizing hormone (LH) like all other glycoprotein hormones is composed of two dissimilar subunits, alpha and beta, that are non-covalently associated. The heterodimer is stabilized by a region of the beta-subunit called the "seatbelt" because it wraps around the alpha-subunit and it is fastened by a disulfide bridge between cysteines beta26 and beta110. Although all 22 cysteines of porcine LH (pLH) are engaged in disulfide bridges, we previously showed that the free cysteine-specific reagent NTCB could react with pLH: it slowly cyanylated two cysteines in pLH and there was a close relationship between NTCB reaction with pLH and association/dissociation kinetics of its subunits. Therefore, cysteines beta26 and beta110 were considered as the best candidates for NTCB reaction. In order to identify the NTCB-reactive cysteines in pLH we have performed a mass spectroscopic analysis of the peptides released after mild basic hydrolysis of S-cyanylated pLH and its subunits. Only cysteines beta100 and beta110 were found to react with NTCB. Since these residues are not linked by a disulfide bridge in the crystallographic 3D structure of gonadotropins, it is proposed that their respective counterparts (Cysbeta93 and beta26) do not react with NTCB either because they are shielded from solvent or because they form a transient bridge. In the first hypothesis, both seatbelt bridges would be independently metastable; in the second one, a fast reversible isomerization between bridges beta26-beta110 and beta93-beta100 would occur. Such a reaction could be catalyzed by the previously recognized intrinsic protein disulfide isomerase (PDI) activity of gonadotropins.

  1. Lutein and brain function

    USDA-ARS?s Scientific Manuscript database

    Lutein is one of the most prevalent carotenoids in nature and in the human diet. Together with zeaxanthin, it is highly concentrated in macular pigment in the foveal retina of primates, attenuating blue light exposure, providing protection from photo-oxidation and enhancing visual performance. Rece...

  2. Circadian Clock genes Per2 and clock regulate steroid production, cell proliferation, and luteinizing hormone receptor transcription in ovarian granulosa cells

    SciTech Connect

    Shimizu, Takashi; Hirai, Yuko; Murayama, Chiaki; Miyamoto, Akio; Miyazaki, Hitoshi; Miyazaki, Koyomi

    2011-08-19

    Highlights: {yields} Treatment with Per2 and Clock siRNAs decreased the number of granulosa cells and LHr expression. {yields}Per2 siRNA treatment did not stimulate the production of estradiol and expression of P450arom. {yields} Clock siRNA treatment inhibited the production of estradiol and expression of P450arom mRNA. {yields}Per2 and Clock siRNA treatment increased and unchanged, respectively, progesterone production in FSH-treated granulosa cells. {yields} The expression of StAR mRNA was increased by Per2 siRNA and unchanged by Clock siRNA. -- Abstract: Circadian Clock genes are associated with the estrous cycle in female animals. Treatment with Per2 and Clock siRNAs decreased the number of granulosa cells and LHr expression in follicle-stimulating hormone FSH-treated granulosa cells. Per2 siRNA treatment did not stimulate the production of estradiol and expression of P450arom, whereas Clock siRNA treatment inhibited the production of estradiol and expression of P450arom mRNA. Per2 and Clock siRNA treatment increased and unchanged, respectively, progesterone production in FSH-treated granulosa cells. Similarly, expression of StAR mRNA was increased by Per2 siRNA and unchanged by Clock siRNA. Our data provide a new insight that Per2 and Clock have different action on ovarian granulosa cell functions.

  3. Comparison between lactating and non-lactating dairy cows on follicular growth and corpus luteum development, and endocrine patterns of ovarian steroids and luteinizing hormone in the estrous cycles.

    PubMed

    Endo, Natsumi; Nagai, Kiyosuke; Tanaka, Tomomi; Kamomae, Hideo

    2012-10-01

    The dynamics of ovarian follicle, corpus luteum (CL), and peripheral plasma ovarian steroids were compared between lactating and non-lactating cows, and a possible association of pulsatile luteinizing hormone (LH) secretion with the dynamics was examined. Lactating (n=5) and non-lactating (n=5) cows were monitored daily for follicle and CL throughout two consecutive estrous cycles (Day 0: day of ovulation). Blood samples were collected daily and at 15 min intervals for 8h on Days 2, 4, 6, 8, and 14 of the second cycle. Lactating cows had larger CL (25.4 ± 1.8mm vs. 23.5 ± 1.5mm, P<0.01) and greater progesterone concentrations (4.6 ± 1.0ng/ml vs. 3.9 ± 0.9 ng/ml, P<0.01) during mid-luteal phase compared with non-lactating cows. Maximal diameters of the first wave dominant follicle (17.2 ± 1.8mm vs. 15.5 ± 0.8mm) and the ovulatory follicle (17.9 ± 1.2mm vs. 15.2 ± 0.8mm) were greater (P<0.05) in lactating cows than in non-lactating cows during the estrous cycles with two follicular waves, but no significant differences were detected between the groups during the estrous cycles with three follicular waves. Plasma estradiol concentrations did not differ between the groups throughout the experiment. Lactating cows had more LH pulses from Days 2 to 14 than non-lactating cows. These results imply that differences in ovarian dynamics may exist between lactating and non-lactating cows, for which the increased number of LH pulses observed in lactating cows may have responsibility.

  4. Molecular biology of channel catfish gonadotropin receptors: 1. Cloning of a functional luteinizing hormone receptor and preovulatory induction of gene expression.

    PubMed

    Kumar, R S; Ijiri, S; Trant, J M

    2001-03-01

    There is little known about the molecular biology of piscine gonadotropin receptors, and information about gene expression during reproductive development is particularly lacking. We have cloned the LH receptor (LHR) in the channel catfish (cc), and examined its gene expression throughout a reproductive cycle. A cDNA encoding the receptor was isolated from the testis using reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends procedures. It encoded a 696-amino acid protein that showed the greatest homology (46-50% identity) with the known LHRs and lesser similarity with FSH receptors and thyroid-stimulating hormone receptors (44-47% and 42-44% identity, respectively). In addition, two characteristics unique to the LHRs were conserved in the cloned receptor and the encoding gene: presence of an intron corresponding to intron 10 in mammals and turkey and occurrence of a double cysteine residue in the cytoplasmic tail for potential palmitoylation. The ccLHR gene was well expressed in the gonads and kidney and merely detectable in the gills, muscle, and spleen. The isolated cDNA encoded an active ccLHR protein, as the recombinant receptor expressed in COS7 cells activated a cAMP response element-driven reporter gene (luciferase) upon exposure to hCG in a dose-dependent manner. Seasonal changes in the ovarian expression of the ccLHR gene, as examined by measuring the transcript abundance by quantitative real-time RT-PCR, remained rather low during most of the reproductive cycle but was acutely induced around the time of spawning. This pattern of expression correlates well with the reported expression of its ligand (LH) in fishes and concurs with the notion that LH is a key regulator of the periovulatory maturational events.

  5. Growth hormone (GH) secretory dynamics in a case of acromegalic gigantism associated with hyperprolactinemia: nonpulsatile secretion of GH may induce elevated insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 levels.

    PubMed

    Yoshida, T; Shimatsu, A; Sakane, N; Hizuka, N; Horikawa, R; Tanaka, T

    1996-01-01

    We describe a case of pituitary gigantism with low levels of growth hormone (GH), elevated insulin-like growth factor-I (IGF-I), and IGF-binding protein-3 (IGF-BP-3). The patient had characteristic clinical features of gigantism and acromegaly. The basal serum GH levels ranged from 1.2-1.9 micrograms/L, which were considered to be within normal limits. Serum GH response to either insulin-induced hypoglycemia or GH-releasing hormone was blunted. Frequent blood samplings during daytime and at night showed nonpulsatile GH secretion. Serum prolactin, IGF-I and IGF-binding protein-3 levels were elevated. After unsuccessful surgery, bromocryptine treatment normalized serum prolactin without affecting serum GH and IGF-I levels. Combined administration of octreotide and bromocryptine reduced serum GH and IGF-I levels. GH bioactivity as measured by Nb2 cell proliferation assay was within reference range. In the present case, nonpulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-I and IGF-BP-3 and cause clinical acromegalic gigantism.

  6. Plasma luteinizing hormone and progesterone in the adult female pig during the oestrous cycles, late pregnancy and lactation, and after ovariectomy and pentobarbitone treatment.

    PubMed

    Parvizi, N; Elsaesser, F; Smidt, D; Ellendorff, F

    1976-05-01

    In a series of experiments on female miniature pigs, the pattern of plasma LH and progesterone levels during the oestrous cycle, late pregnancy and lactation and after ovariectomy were characterized, and the effect of pentobarbitone treatment was tested. The preovulatory surge of LH occurred in seven out of eight animals between 00.00 and 12.0 h on day 0 of the oestrous cycle (day 1 of standing heat). Plasma progesterone strated to decline 8 days before oestrus and reached its lowest value 5 days before the preovulatory LH peak. Increases in progesteron concentration were already noticeable 48 h after the LH surge. During late pregnancy, parturition and lactation, plasma LH was low and showed only minor fluctuations, while plasma progesterone declined 4 to 5 days before parturition. Both hormones remained at low levels throughout lactation. Three weeks before parturition increases in LH were always followed by an increase in progesterone. This dependency was greatly diminished immediately before delivery. Four to 12 days after weaning the animals came into oestrus which was followed by an increase in LH and later an increase in progesterone concentrations. Ovariectomy during dioestrus resulted in a steady increase in plasma LH levels of 35-39 days. Ovariectomy caused abortion if performed on day 100 of pregnancy. It was followed by a rapid increase of plasma LH concentration. Normal parturition (around day 115) and lactation took place when animals were spayed on day 112 of pregnancy. In this case, plasma LH levels remained even lower than before ovariectomy as long as lactation was maintained. Immediately after weaning a rapid increase in the normal postovariectomy pattern of LH secretion was observed. Pentobarbitone anaesthesia (30-35 mg/kg body wt, initial dose), during pro-oestrusoestrus, for less than 5 h had no effect on the preovulatory LH increase. However, pentobarbitone anaesthesia for more than 6 h inhibitied the LH peak and ovulation if the animal was

  7. A preponderance of basic luteinizing hormone (LH) isoforms accompanies inappropriate hypersecretion of both basal and pulsatile LH in adolescents with polycystic ovarian syndrome.

    PubMed

    Ropelato, M G; Garcia-Rudaz, M C; Castro-Fernandez, C; Ulloa-Aguirre, A; Escobar, M E; Barontini, M; Veldhuis, J D

    1999-12-01

    We recently demonstrated that adolescent girls with polycystic ovarian syndrome (PCOS) exhibit augmented LH secretion due to an increase in immunofluorometric and deconvolution-estimated LH secretory burst mass and pulse frequency. Concurrently, we inferred either a prolongation of apparent (endogenous) LH half-life or elevated basal (nonpulsatile) LH release in PCOS. The in vivo half-life of LH molecules can be affected by the oligosaccharide side-chains, which also modify in vitro bioactivity and electrostatic change. Accordingly, as a surrogate estimator of altered endogenous LH half-life and/or biopotency in PCOS, we characterized the isoelectric properties of secreted LH isoforms and determined their in vitro biological activity in adolescent girls with PCOS compared with healthy age-matched eumenorrheic controls. To this end, 12-h (overnight) serum samples from PCOS patients (n = 12) and normal adolescents (n = 10) were pooled by subject. Bioactive LH concentrations were then quantitated in a rat Leydig cell in vitro bioassay, and immunological activity was determined by immunofluorometry. The distribution of LH isoforms was evaluated by preparative chromatofocusing (pH window, 10.5 to <4.0) of samples further combined to yield three independent serum pools for each of the patient and control groups. Fasting serum concentrations of 17-hydroxyprogesterone (17-OHP), androstenedione, testosterone, estrone, estradiol, and sex hormone-binding globulin were determined as possible endocrine correlates of LH isotypes. Mean serum concentrations of immunoreactive and bioactive LH in adolescents with PCOS were 3 and 2 times higher than values in controls: immunoreactive: PCOS, 7.8+/-0.9; controls: 2.6+/-0.3 IU/L (P < 0.001); and bioactive: PCOS, 52+/-10; controls, 25+/-4.1 IU/L (P = 0.002), respectively. Bioactive LH concentrations correlated positively with 17-OHP (P = 0.022), androstenedione (P = 0.012), and testosterone (P = 0.046) concentrations in PCOS

  8. Luteal expression of cytochrome P450 side-chain cleavage, steroidogenic acute regulatory protein, 3beta-hydroxysteroid dehydrogenase, and 20alpha-hydroxysteroid dehydrogenase genes in late pregnant rats: effect of luteinizing hormone and RU486.

    PubMed

    Stocco, C O; Chedrese, J; Deis, R P

    2001-10-01

    A decrease in serum progesterone at the end of pregnancy is essential for the induction of parturition in rats. We have previously demonstrated that LH participates in this process through: 1) inhibiting 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity and 2) stimulating progesterone catabolism by inducing 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) activity. The objective of this investigation was to determine the effect of LH and progesterone on the luteal expression of the steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450(scc)), 3beta-HSD, and 20alpha-HSD genes. Gene expression was analyzed by Northern blot analysis 24 and 48 h after administration of LH or vehicle on Day 19 of pregnancy. StAR and 3beta-HSD mRNA levels were lower in LH-treated rats than in rats administered with vehicle at both time points studied. P450(scc) mRNA levels were unaffected by LH. The 20alpha-HSD mRNA levels were not different between LH and control rats 24 h after treatment; however, greater expression of 20alpha-HSD, with respect to controls, was observed in LH-treated rats 48 h after treatment. Luteal progesterone content dropped in LH-treated rats at both time points studied, whereas serum progesterone decreased after 48 h only. In a second set of experiments, the anti-progesterone RU486 was injected intrabursally on Day 20 of pregnancy. RU486 had no effect on 3beta-HSD or P450(scc) expression but increased 20alpha-HSD mRNA levels after 8 h treatment. In conclusion, the luteolytic effect of LH is mediated by a drop in StAR and 3beta-HSD expression without effect on P450(scc) expression. We also provide the first in vivo evidence indicating that a decrease in luteal progesterone content may be an essential step toward the induction of 20alpha-HSD expression at the end of pregnancy in rats.

  9. Hormones

    MedlinePlus

    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, ...

  10. Comparison of luteinizing hormone, leptin and progesterone levels in the systemic circulation (Vena jugularis) and near the ovarian circulation (Vena cava caudalis) during the oestrous cycle in Mangalica and Landrace gilts.

    PubMed

    Brüssow, Klaus-Peter; Schneider, Falk; Tuchscherer, Armin; Egerszegi, Istvan; Rátky, Jozsef

    2008-12-01

    The objective of this study was to evaluate luteinizing hormone (LH) and luteal progesterone (P4) secretion in systemic blood and blood near the ovaries in Mangalica (M) and Landrace (L) gilts by implanting catheters into the Vena jugularis and the Vena cava caudalis via the Vena saphena, respectively. Furthermore, leptin was analyzed in jugular vein blood. Blood was collected twice daily from day 7 to day 19 of the oestrous cycle and frequently (10-min intervals for 6 h) on day 9, day 12 and day 15 in M (n=3) and L gilts (n=4). L gilts had congruent pulsatile LH secretion in both veins, but the LH concentrations in M were always below the assay sensitivity during the luteal phase. In both breeds, episodic P4 secretion was found in the jugular and caval veins, and both sampling site and breed had an influence on P4 secretion (P<0.05). The mean concentration of P4 was higher (P<0.01) in utero-ovarian blood (75.8+/-5.3 in M; 49.6+/-4.2 ng/ml in L) than in the periphery (31.3+/-2.0 in M; 21.2+/-1.8 ng/ml in L). M pigs had a lower number of corpora lutea (9.7+/-2.3 vs. 20.5+/-4.4), and analysis of the P4 secretion ratio per corpus luteum revealed an influence of breed (P<0.01). This ratio was significantly higher in M (3.8+/-0.3 and 8.7+/-0.7 ng/ml) compared with the L gilts (1.4+/-0.1 and 2.8+/-0.3 ng/ml) in the jugular and caval veins, respectively. Blood sampling from the Vena cava caudalis is potentially more precise than from the Vena jugularis for evaluation of ovarian P4 secretion. Both the higher P4 concentration and increased leptin secretion (11.3+/-0.6 vs. 3.0+/-0.1 ng/ml, P<0.05) and consequently the altered LH secretion pattern in the Mangalica may contribute to the lower fecundity of this breed.

  11. Effect of recombinant human follicle-stimulating hormone and luteinizing hormone on in vitro maturation of porcine oocytes evaluated by the subsequent in vitro development of embryos obtained by in vitro fertilization, intracytoplasmic sperm injection, or parthenogenetic activation.

    PubMed

    Silvestre, M A; Alfonso, J; García-Mengual, E; Salvador, I; Duque, C C; Molina, I

    2007-05-01

    The aim of this work was to study the effect of recombinant human (rh) FSH and LH on in vitro maturation of pig oocytes compared with a conventional hormonal supplement based on equine (PMSG) and human chorionic gonadotropins (hCG), as evaluated by the developmental ability of 3 types of pig embryos obtained by in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), or artificial activation (ATA). In Exp. 1, one cumulus-oocyte complex group (A group) was supplemented with rh-FSH and rh-LH (0.1 IU/mL each), and the other group (B group) was supplemented with PMSG and hCG (10 IU/mL each). No differences in nuclear maturation between the A and B groups were observed (68.5 vs. 71.4%, respectively). No differences were detected between hormonal treatments in the rates of cleavage or blastocyst formation of ATA, IVF, and ICSI embryos. Total cell number of the embryos was not significantly different in any experimental group (A: 31.1, 28.5, and 19.8 vs. B: 25.2, 25.5, and 20.6 for ATA, IVF, and ICSI embryos, respectively). In Exp. 2, the effects of different concentrations of rh-FSH and rh-LH (0.5, 0.1, or 0.05 IU/mL) in maturation medium on nuclear maturation and in vitro development of embryos obtained by IVF were studied. No effect of different hormonal concentrations on blastocyst formation rates was observed (8.5, 13.0, and 5.7%, respectively). Blastocyst cell number was not different in any experimental group. In conclusion, the results obtained here permit us to substitute PMSG and hCG with rh-FSH and rh-LH and to produce pig embryos obtained by IVF, ICSI, or ATA.

  12. Comparison of macular pigment and serum lutein concentration changes between free lutein and lutein esters supplements in Japanese subjects.

    PubMed

    Yoshizako, Hiroko; Hara, Katunori; Takai, Yasuyuki; Kaidzu, Sachiko; Obana, Akira; Ohira, Akihiro

    2016-09-01

    To compare changes in macular pigment optical density (MPOD) and serum lutein concentration between free lutein and lutein esters supplements in healthy Japanese individuals. Twenty healthy subjects (age range, 22-47 years) were recruited into this prospective, randomized, doubled-blind comparative study. Individuals were evenly divided into two groups: free lutein group, supplementation with 10 mg of free lutein; or lutein esters group, supplementation with 20 mg of lutein esters equivalent to 10 mg of free lutein. Each participant took either type of oral lutein daily for 3 months. The serum lutein concentrations and MPOD levels were measured at baseline and 3 and 6 months after the start of supplementation. There were no significant differences in the serum lutein concentrations and MPOD levels at baseline between the groups. The increased serum lutein concentration and MPOD levels at 3 months were respectively, 89% and 38% in the free lutein group and 97% and 17% in the lutein esters group. The serum lutein concentrations in both groups and MPOD levels in the free lutein group increased significantly (p < 0.05) from baseline. No significant differences in serum lutein concentrations and MPOD levels were seen between the groups. Three months after supplementation ended, the serum lutein concentration decreased; the MPOD remained elevated in both groups. The serum lutein concentrations and MPOD levels increased significantly with either free lutein or lutein esters, and no significant differences were found between the two. Both were considered useful as lutein supplements. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  13. Subsets of gonadotropin-releasing hormone (GnRH) neurons are activated during a steroid-induced luteinizing hormone surge and mating in mice: a combined retrograde tracing double immunohistochemical study.

    PubMed

    Rajendren, G

    2001-11-09

    The decapeptide gonadotropin-releasing hormone (GnRH) plays a pivotal role in reproduction and is synthesized by GnRH-producing cell bodies in the basal forebrain. Experiments were designed to investigate whether GnRH cells projecting outside the blood brain barrier or those projecting within the brain are activated during the steroid-induced LH surge or mating in female mice. Retrograde uptake of intraperitoneally administered fluorogold (FG) by GnRH cells and double immunostaining for GnRH and Fos was employed for this purpose. The number of GnRH cells with FG uptake was comparable among the surged, mated and control mice. However, the number of Fos-positive GnRH cells was significantly higher in the steroid-induced LH surge group than in the mated mice. The number of Fos+FG-positive GnRH cells was higher and the number of FG-only GnRH cells was lower in mice with a steroid-induced LH surge as compared with the mated mice. This suggests the existence of a subgroup of GnRH cells projecting outside the blood-brain barrier activated during the steroid-induced LH surge but not during mating. The activation of similar proportions of GnRH cells without FG uptake in both the mated and the surge group indicate that nonneuroendocrine GnRH cells are not silent but can be activated by both mating and steroid hormones. Thus, functional subgroups may exist within the GnRH system with considerable overlap in the input to these cells.

  14. Bioavailability and biodistribution of nanodelivered lutein

    USDA-ARS?s Scientific Manuscript database

    The aim of the study was to evaluate the ability of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to enhance lutein bioavailability. The bioavailability of free lutein and PLGA-NP lutein in rats was assessed by determining plasma pharmacokinetics and deposition in selected tissues. Lutein ...

  15. Estrogen receptor immunoreactivity is present in the majority of central histaminergic neurons: evidence for a new neuroendocrine pathway associated with luteinizing hormone-releasing hormone-synthesizing neurons in rats and humans.

    PubMed

    Fekete, C S; Strutton, P H; Cagampang, F R; Hrabovszky, E; Kalló, I; Shughrue, P J; Dobó, E; Mihály, E; Baranyi, L; Okada, H; Panula, P; Merchenthaler, I; Coen, C W; Liposits, Z S

    1999-09-01

    The central regulation of the preovulatory LH surge requires a complex sequence of interactions between neuronal systems that impinge on LH-releasing hormone (LHRH)-synthesizing neurons. The reported absence of estrogen receptors (ERs) in LHRH neurons indicates that estrogen-receptive neurons that are afferent to LHRH neurons are involved in mediating the effects of this steroid. We now present evidence indicating that central histaminergic neurons, exclusively located in the tuberomammillary complex of the caudal diencephalon, serve as an important relay in this system. Evaluation of this system revealed that 76% of histamine-synthesising neurons display ERalpha-immunoreactivity in their nucleus; furthermore histaminergic axons exhibit axo-dendritic and axo-somatic appositions onto LHRH neurons in both the rodent and the human brain. Our in vivo studies show that the intracerebroventricular administration of the histamine-1 (H1) receptor antagonist, mepyramine, but not the H2 receptor antagonist, ranitidine, can block the LH surge in ovariectomized estrogen-treated rats. These data are consistent with the hypothesis that the positive feedback effect of estrogen in the induction of the LH surge involves estrogen-receptive histamine-containing neurons in the tuberomammillary nucleus that relay the steroid signal to LHRH neurons via H1 receptors.

  16. Disruption of Zebrafish Follicle-Stimulating Hormone Receptor (fshr) But Not Luteinizing Hormone Receptor (lhcgr) Gene by TALEN Leads to Failed Follicle Activation in Females Followed by Sexual Reversal to Males.

    PubMed

    Zhang, Zhiwei; Lau, Shuk-Wa; Zhang, Lingling; Ge, Wei

    2015-10-01

    Gonadotropins are primary hormones that control vertebrate reproduction. In a recent study, we analyzed the impacts of FSH and LH on zebrafish reproduction by disrupting FSH and LH-β genes (fshb and lhb) using transcription activator-like effector nuclease (TALEN) technology. Using the same approach, we successfully deleted FSH and LH receptor genes (fshr and lhcgr) in the present study. In contrast to the deficiency of its cognate ligand FSH, the fshr-deficient females showed a complete failure of follicle activation with all ovarian follicles arrested at the primary growth-previtellogenic transition, which is the marker for puberty onset in females. Interestingly, after blockade at the primary growth stage for varying times, all females reversed to males, and all these males were fertile. In fshr-deficient males, spermatogenesis was normal in adults, but the initiation of spermatogenesis in juveniles was retarded. In contrast to fshr, the deletion of the lhcgr gene alone caused no obvious phenotypes in both males and females; however, double mutation of fshr and lhcgr resulted in infertile males. In summary, our results in the present study showed that Fshr was indispensable to folliculogenesis and the disruption of the fshr gene resulted in a complete failure of follicle activation followed by masculinization into males. In contrast, lhcgr does not seem to be essential to zebrafish reproduction in both males and females. Neither Fshr nor Lhcgr deficiency could phenocopy the deficiency of their cognate ligands FSH and LH, which is likely due to the fact that Fshr can be activated by both FSH and LH in the zebrafish.

  17. High serum luteinizing hormone levels induce ovarian delta4 cytochrome P450c17alpha down-regulation in hirsute women: complete effect on 17-hydroxylase and partial effect on 17,20-lyase.

    PubMed

    Rieu, M; Mourrieras, F; Riveline, J P; Laplanche, S; Both, D; Kuhn, J M

    1998-09-01

    It is well known that normal and mildly elevated luteinizing hormone (LH) levels induce increased activity of ovarian 17-hydroxylase and 17,20-lyase, the cytochrome P450cl7alpha (P450) enzymes. This leads to increased ovarian 17alpha-hydroxyprogesterone (17-OHP) and androstenedione production. In contrast, it has been shown in both in vitro and in vivo studies in animals and in in vitro studies in women that high LH concentrations have opposite effects on these enzymes. These LH down-regulating effects appear to be more marked on 17,20-lyase than on 17-hydroxylase. Finally, these LH effects have not been reported in vivo in women. Therefore, we investigated the relationships between serum LH levels and serum 17-OHP and androstenedione concentrations in 263 consecutive hirsute women (HW) with normal serum 17-OHP responses to acute adrenocorticotropin (ACTH) stimulation. The patterns of basal serum steroid concentrations differed according to the basal serum LH levels. Indeed, for relationships between LH and 17-OHP concentrations, a positive correlation (P < 0.001) was found between the levels of these parameters when LH levels ranged from 0.2 to 9.0 IU/l. Conversely, for LH levels greater than 9.0 to 21.0 IU/l, LH values were negatively correlated (P<0.001) with 17-OHP concentrations. Similar results were observed for relationships between LH and androstenedione levels but the LH peak level related to decreasing androstenedione concentrations was 12.0 IU/l. Finally, the mean 17-OHP level in patients with LH levels which induced marked P450 down-regulation (i.e. more than 12 IU/l) was similar to that in patients with LH levels within the normal range (i.e. less than 6 IU/l). In contrast, the mean androstenedione level in the former patients was markedly higher (P<0.001) than that in the latter patients. In conclusion, as previously reported in in vitro studies, this in vivo study indicates that LH induces stimulating and down-regulating effects on both ovarian delta

  18. Effects of acute feed restriction combined with targeted use of increasing luteinizing hormone content of follicle-stimulating hormone preparations on ovarian superstimulation, fertilization, and embryo quality in lactating dairy cows.

    PubMed

    Bender, R W; Hackbart, K S; Dresch, A R; Carvalho, P D; Vieira, L M; Crump, P M; Guenther, J N; Fricke, P M; Shaver, R D; Combs, D K; Wiltbank, M C

    2014-02-01

    Multiple metabolic and hormonal factors can affect the success of protocols for ovarian superstimulation. In this study, the effect of acute feed restriction and increased LH content in the superstimulatory FSH preparation on numbers of ovulations, fertilization, and embryo quality in lactating dairy cows was evaluated. Two experiments were performed using a Latin square design with treatments arranged as a 2 × 2 factorial: feed restriction (FR; 25% reduction in dry matter intake) compared with ad libitum (AL) feeding, combined with high (H) versus low (L) LH in the last 4 injections of the superstimulatory protocol. As expected, FR decreased circulating insulin concentrations (26.7 vs. 46.0 μU/mL). Two analyses were performed: one that evaluated the complete Latin square in experiment 2 and a second that evaluated only the first periods of experiments 1 and 2. For both analyses, follicle numbers, ovulation rates, and corpora lutea on d 7 were not different. In the first period analysis of experiments 1 and 2, we observed an interaction between feed allowance and amount of LH on fertilization rates, percentage of embryos or oocytes that were quality 1 and 2 embryos, and number of embryos or oocytes that were degenerate. Fertilization rates were greater for the AL-L (89.4%) and FR-H (80.1%) treatments compared with the AL-H (47.9%) and FR-L (59.9%) treatments. Similarly, the proportion of total embryos or oocytes designated as quality 1 and 2 embryos was greater for AL-L (76.7%) and FR-H (73.4%) treatments compared with AL-H (35.6%) and FR-L (47.3%) treatments. In addition, the number of degenerate embryos was decreased for AL-L (1.3) and FR-H (0.4) treatments compared with the AL-H (2.6) and FR-L (2.3) treatments. Thus, cows with either too low (FR-L) or too high (AL-H) insulin and LH stimulation had lesser embryo production after superstimulation because of reduced fertilization rate and increased percentage of degenerate embryos. Therefore, interaction of the

  19. Induction of follicular luteinization by equine chorionic gonadotropin in cyclic guinea pigs.

    PubMed

    Li, Jun-rong; Wang, Wei; Shi, Fang-xiong

    2015-12-01

    The effects of equine chorionic gonadotropin (eCG) on follicular development and ovulation in cyclic guinea pigs were investigated by histological and immunohistochemical analyses. Three groups of guinea pigs (n=12) were administrated subcutaneously with saline, 20 or 50 IU of eCG, respectively, on cyclic Day 12 (Day 1=vaginal openings). Ovaries were collected at 4 and 8 d after administration (6 animals per group each time). The eCG administration induced significant and distinct morphological changes in the ovaries, as it promoted the luteinization of granulosa cells, but not follicular development. In addition, proliferating cell nuclear antigen (PCNA) and steroidogenic acute regulatory protein (StAR) were immunolocalized specifically in luteinized follicles. Our experiments together indicate that eCG administration can induce follicular luteinization but not superovulation in guinea pigs. The eCG in cyclic guinea pigs functions similar to that of luteinizing hormone (LH), but not follicle-stimulating hormone (FSH).

  20. Induction of follicular luteinization by equine chorionic gonadotropin in cyclic guinea pigs*

    PubMed Central

    Li, Jun-rong; Wang, Wei; Shi, Fang-xiong

    2015-01-01

    The effects of equine chorionic gonadotropin (eCG) on follicular development and ovulation in cyclic guinea pigs were investigated by histological and immunohistochemical analyses. Three groups of guinea pigs (n=12) were administrated subcutaneously with saline, 20 or 50 IU of eCG, respectively, on cyclic Day 12 (Day 1=vaginal openings). Ovaries were collected at 4 and 8 d after administration (6 animals per group each time). The eCG administration induced significant and distinct morphological changes in the ovaries, as it promoted the luteinization of granulosa cells, but not follicular development. In addition, proliferating cell nuclear antigen (PCNA) and steroidogenic acute regulatory protein (StAR) were immunolocalized specifically in luteinized follicles. Our experiments together indicate that eCG administration can induce follicular luteinization but not superovulation in guinea pigs. The eCG in cyclic guinea pigs functions similar to that of luteinizing hormone (LH), but not follicle-stimulating hormone (FSH). PMID:26642181

  1. Structure of the lutein-binding domain of human StARD3 at 1.74 Å resolution and model of a complex with lutein

    SciTech Connect

    Horvath, Martin P. George, Evan W.; Tran, Quang T.; Baumgardner, Kody; Zharov, Gabe; Lee, Sarah; Sharifzadeh, Hassan; Shihab, Saeed; Mattinson, Ty; Li, Binxing; Bernstein, Paul S.

    2016-07-27

    The structure of a START-domain protein known to bind lutein in the human retina is reported to an improved resolution limit. Rigid-body docking demonstrates that at least a portion of lutein must protrude from the large tunnel-like cavity characteristic of this helix-grip protein and suggests a mechanism for lutein binding specificity. A crystal structure of the lutein-binding domain of human StARD3 (StAR-related lipid-transfer protein 3; also known as MLN64) has been refined to 1.74 Å resolution. A previous structure of the same protein determined to 2.2 Å resolution highlighted homology with StARD1 and shared cholesterol-binding character. StARD3 has since been recognized as a carotenoid-binding protein in the primate retina, where its biochemical function of binding lutein with specificity appears to be well suited to recruit this photoprotective molecule. The current and previous structures correspond closely to each other (r.m.s.d. of 0.25 Å), especially in terms of the helix-grip fold constructed around a solvent-filled cavity. Regions of interest were defined with alternate conformations in the current higher-resolution structure, including Arg351 found within the cavity and Ω1, a loop of four residues found just outside the cavity entrance. Models of the complex with lutein generated by rigid-body docking indicate that one of the ionone rings must protrude outside the cavity, and this insight has implications for molecular interactions with transport proteins and enzymes that act on lutein. Interestingly, models with the ∊-ionone ring characteristic of lutein pointing towards the bottom of the cavity were associated with fewer steric clashes, suggesting that steric complementarity and ligand asymmetry may play a role in discriminating lutein from the other ocular carotenoids zeaxanthin and meso-zeaxanthin, which only have β-ionone rings.

  2. A pilot comparison of phospolipidated lutein to conventional lutein for effects on plasma lutein concentrations in adult people.

    PubMed

    DiSilvestro, Robert A; Thomas, Sara; Harrison, Earl; Epitropoulos, Alice

    2015-10-07

    The percent absorption of lutein from supplements falls well below that from lutein enriched egg yolk, a rich source of phospholipids. Therefore, a supplement of lutein plus phospholipids was tested for effects on serum accumulation. A 10 day supplementation with a solid-lipid particle (SLP) lutein complex or conventional lutein ester was done in apparently healthy people (both supplement types taken with fat containing meals). Plasma lutein was measured pre- and post-supplementation as well as 7 days after supplementation stopped. Changes within each supplement group were analyzed by paired t-test; group comparisons were done by unpaired t-test. The solid-lipid particle complex lutein gave much higher plasma lutein values than conventional lutein ester. The lutein complex showed superior effects based on absolute mean value after 10 days of supplementation, change in value from baseline to 10 days, and value at 7 days after supplement discontinuation. A solid lipid lutein complex strongly increased plasma lutein levels compared to a conventional form.

  3. Photoacoustic measurement of lutein in biological matrix

    NASA Astrophysics Data System (ADS)

    Bicanic, D.; Luterotti, S.; Becucci, M.; Fogliano, V.; Versloot, P.

    2005-06-01

    Photoacoustic (PA) spectroscopy was applied for the first time to quantify lutein in a complex biological matrix. Standard addition of lutein to a biological low-lutein matrix was used for the calibration. The PA signal was found linearly proportional (R > 0.98) to lutein concentration up to 0.3% (w/w). The dynamic range of concentrations extends to 1% (w/w) lutein. For a given experimental set-up the responsivity of PA detector within the range of linearity was estimated to 1.1 mV/1% lutein. Precision of repeated analyses is good with average RSD values of 4 and 5% for blanks and spiked samples, respectively. The analytical parameters indicate that the PA method is fast and sensitive enough for quantification of lutein in supplementary drugs and in the lutein-rich foods.

  4. Effect of Chlorotriazine Pesticides on Gonadotrophin Releasing Hormone in the Neuronal GT1-7 Cell Line and Hypothalamic Explants

    EPA Science Inventory

    Gonadotrophin releasing hormone (GnRH) stimulates the release of pituitary luteinizing hormone (LH) and follicle stimulating hormone. These pituitary hormones are necessary for normal reproductive function in both males and females. It is well recognized that disruption of nor...

  5. Effect of Chlorotriazine Pesticides on Gonadotrophin Releasing Hormone in the Neuronal GT1-7 Cell Line and Hypothalamic Explants

    EPA Science Inventory

    Gonadotrophin releasing hormone (GnRH) stimulates the release of pituitary luteinizing hormone (LH) and follicle stimulating hormone. These pituitary hormones are necessary for normal reproductive function in both males and females. It is well recognized that disruption of nor...

  6. Bioavailability and biodistribution of nanodelivered lutein.

    PubMed

    Kamil, Alison; Smith, Donald E; Blumberg, Jeffrey B; Astete, Carlos; Sabliov, Cristina; Oliver Chen, C-Y

    2016-02-01

    The aim of the study was to evaluate the ability of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to enhance lutein bioavailability. The bioavailability of free lutein and PLGA-NP lutein in rats was assessed by determining plasma pharmacokinetics and deposition in selected tissues. Lutein uptake and secretion was also assessed in Caco-2 cells. Compared to free lutein, PLGA-NP increased the maximal plasma concentration (Cmax) and area under the time-concentration curve in rats by 54.5- and 77.6-fold, respectively, while promoting tissue accumulation in the mesenteric fat and spleen. In comparison with micellized lutein, PLGA-NP lutein improved the Cmax in rat plasma by 15.6-fold and in selected tissues by ⩾ 3.8-fold. In contrast, PLGA-NP lutein had a lower uptake and secretion of lutein in Caco-2 cells by 10.0- and 50.5-fold, respectively, compared to micellized lutein. In conclusion, delivery of lutein with polymeric NP may be an approach to improve the bioavailability of lutein in vivo. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Human anti-luteinizing hormone-releasing hormone antibodies in patients treated with synthetic luteinizing hormone-releasing hormone

    SciTech Connect

    Meakin, J.L.; Keogh, E.J.; Martin, C.E.

    1985-05-01

    One hundred sixty-three patients who were given synthetic LH-RH therapeutically underwent monitoring of serum IgG anti-LH-RH antibodies. Five of the patients showed specific binding to antibodies. Development of anti-LH-RH antibodies was not limited to those patients with a congenital deficiency of LH-RH. Urticarial responses occurred in four patients, only one of whom had IgG antibodies. Patients who had IgG antibodies or an urticarial response underwent monitoring of their serum IgE anti-LH-RH antibodies, but none had a positive binding response. The refractory state which has been reported in patients in whom similar antibodies to LH-RH develop was not invariably observed among these patients.

  8. Characterization of milk proteins-lutein complexes and the impact on lutein chemical stability.

    PubMed

    Yi, Jiang; Fan, Yuting; Yokoyama, Wallace; Zhang, Yuzhu; Zhao, Liqing

    2016-06-01

    In this study, the interaction of WPI (whey protein isolate) and SC (sodium caseinate) with hydrophobic lutein was investigated through UV-vis spectroscopy and circular dichroism (CD) as well as fluorescence. The effects on lutein's chemical stability were also examined. The decrease of turbidity of lutein suggested that lutein's aqueous solubility was improved after binding with milk proteins. CD analysis indicated lutein had little impact on the secondary structures of both proteins. Different preparation methods have significant impacts on the binding constant. Fluorescence results indicated that WPI and SC interact with lutein by hydrophobic contacts. Milk proteins have protective effects on lutein against oxidation and decomposition, and SC showed better capability in protecting lutein from oxidation than WPI during 16 days storage. The lutein's chemical stability was increased with increasing of proteins concentration. The results indicated that milk proteins may act as effective carriers for lipophilic nutraceuticals.

  9. Environmental Effects on Lutein Concent and Relationship of Lutein and Other Seed Components in Soybean

    USDA-ARS?s Scientific Manuscript database

    Lutein is a major carotenoid in soybean [Glycine max (L.) Merr. ] seed, and has been shown to be beneficial for eye health in humans. Development of soybeans high in lutein is a goal of some breeding programs. Little is known about how different growing environments affect lutein concentration. Obje...

  10. The Tissue Distribution of Lutein in Laying Hens Fed Lutein Fortified Chlorella and Production of Chicken Eggs Enriched with Lutein

    PubMed Central

    An, Byoung-Ki; Jeon, Jin-Young; Kang, Chang-Won; Kim, Jin-Man

    2014-01-01

    Two experiments were conducted to investigate the dietary effects of conventional or lutein fortified chlorella on lutein absorptions, the tissue distributions and the changes in lutein content of eggs in laying hens. In Exp 1, a total of one hundred and fifty, 70 wk-old Hy-Line brown layers were divided into three groups with five replicates and fed with each experiment diet (control diet, diet with 1% conventional chlorella or lutein fortified chlorella) for 2 wk, respectively. The egg production in groups fed diets containing both chlorella powders were higher than that of the control group (p<0.01). With chlorella supplementations, the yolk color significantly increased, although there were no significant differences in the eggshell qualities. The lutein contents of serum, liver and growing oocytes were greatly increased by feeding conventional or lutein fortified chlorella (p<0.01). In Exp. 2, a total of ninety 60 wk-old Hy-Line brown layers were assigned into three groups with three replicates per group (10 birds per replicate). The birds were fed with one of three experimental diets (0, 0.1 or 0.2% lutein fortified chlorella) for 2 wk, respectively. The egg production was not affected by dietary treatments. The egg weight in the group fed with diet containing 0.2% of lutein fortified chlorella was higher than that of the control (p<0.05). As the dietary chlorella levels increased, the daily egg mass linearly increased, although not significantly. The yolk colors in groups fed diets containing lutein fortified chlorella were dramatically increased as compared to the control (p<0.001). The lutein in chicken eggs significantly increased when fed with 0.2% of lutein fortified chlorella (p<0.01). These results suggested that the dietary lutein derived from chlorella was readily absorbed into the serum and absorbed by the liver with growing oocyte for commercial laying hens. Particularly, the lutein fortified chlorella was a valuable natural source for the

  11. The Tissue Distribution of Lutein in Laying Hens Fed Lutein Fortified Chlorella and Production of Chicken Eggs Enriched with Lutein.

    PubMed

    An, Byoung-Ki; Jeon, Jin-Young; Kang, Chang-Won; Kim, Jin-Man; Hwang, Jae-Kwan

    2014-01-01

    Two experiments were conducted to investigate the dietary effects of conventional or lutein fortified chlorella on lutein absorptions, the tissue distributions and the changes in lutein content of eggs in laying hens. In Exp 1, a total of one hundred and fifty, 70 wk-old Hy-Line brown layers were divided into three groups with five replicates and fed with each experiment diet (control diet, diet with 1% conventional chlorella or lutein fortified chlorella) for 2 wk, respectively. The egg production in groups fed diets containing both chlorella powders were higher than that of the control group (p<0.01). With chlorella supplementations, the yolk color significantly increased, although there were no significant differences in the eggshell qualities. The lutein contents of serum, liver and growing oocytes were greatly increased by feeding conventional or lutein fortified chlorella (p<0.01). In Exp. 2, a total of ninety 60 wk-old Hy-Line brown layers were assigned into three groups with three replicates per group (10 birds per replicate). The birds were fed with one of three experimental diets (0, 0.1 or 0.2% lutein fortified chlorella) for 2 wk, respectively. The egg production was not affected by dietary treatments. The egg weight in the group fed with diet containing 0.2% of lutein fortified chlorella was higher than that of the control (p<0.05). As the dietary chlorella levels increased, the daily egg mass linearly increased, although not significantly. The yolk colors in groups fed diets containing lutein fortified chlorella were dramatically increased as compared to the control (p<0.001). The lutein in chicken eggs significantly increased when fed with 0.2% of lutein fortified chlorella (p<0.01). These results suggested that the dietary lutein derived from chlorella was readily absorbed into the serum and absorbed by the liver with growing oocyte for commercial laying hens. Particularly, the lutein fortified chlorella was a valuable natural source for the

  12. Bioavailability of lutein in corn distillers dried grains with solubles relative to lutein in corn gluten meal based on lutein retention in egg yolk.

    PubMed

    Shin, Hye Seong; Kim, Jong Woong; Lee, Dong Gu; Lee, Sanghyun; Kil, Dong Yong

    2016-08-01

    Dietary lutein and its food sources have gained great attention due to its health-promoting effects on humans, especially for certain eye diseases. However, relative bioavailability (RBV) of lutein among lutein-rich feed ingredients that lead to lutein-enriched egg production has not been determined. Thus, the RBV of lutein in corn distillers dried grains with solubles (DDGS) as compared to lutein in corn gluten meal (CGM) was evaluated based on lutein retention in egg yolk. Increasing inclusion levels of DDGS or CGM in diets increased (linear, P < 0.01) Roche colour score and lutein concentrations of egg yolk without affecting laying performance. Multiple regression analysis revealed that the bioavailability of lutein in DDGS was less (P < 0.05) than that of lutein in CGM, with the RBV of lutein in DDGS being 61.6% when the bioavailability of lutein in CGM was assumed to be 100% for lutein retention in egg yolk. The results of the present experiment indicate that the DDGS can be a potential ingredient for laying hens to improve egg yolk colour and lutein concentrations of egg yolk although lutein in DDGS is less bioavailable than lutein in CGM. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  13. Absorption and ocular deposition of dietary lutein in marine mammals.

    PubMed

    Koutsos, Elizabeth A; Schmitt, Todd; Colitz, Carmen M H; Mazzaro, Lisa

    2013-01-01

    Cataracts and ocular disease are common lesions of marine mammals in zoological collections. Lutein, an oxygenated carotenoid, may have therapeutic or prophylactic effects on ocular disorder. Therefore, this study examined the ability of marine mammals to absorb dietary lutein. Two preliminary trials examined lutein in two forms (beadlet or ester) in a small sample size of marine mammals representing pinnipeds and cetaceans. Lutein was fed daily in tablets providing 0.89-3.6 mg lutein/kg body weight(0.75) per day for 15 days to 2 years. A third study was conducted using lutein beadlet fed at 3.6 mg lutein/kg body weight(0.75) per day for 15-21 days. Blood was analyzed for lutein pre- and postsupplementation. In the preliminary trials, lutein beadlet was observed to result in greater blood lutein levels than lutein esters, and cetaceans had more noticeable responses than pinnipeds. In Study 3, serum lutein and zeaxanthin increased postsupplementation in beluga whales (P < 0.05), and serum lutein tended to increase postsupplementation in dolphins (P < 0.10), but little change was seen in serum lutein in pinnipeds or manatee. Opportunistic retinal samples demonstrated some detectable lutein in the retina of a dolphin and several harp seals. The lutein levels in dolphins after supplementation are similar to those reported in free-ranging animals. Ocular lutein in harp seals demonstrates that ocular deposition occurs despite low circulating lutein levels.

  14. Structure of the lutein-binding domain of human StARD3 at 1.74 Å resolution and model of a complex with lutein

    PubMed Central

    Horvath, Martin P.; George, Evan W.; Tran, Quang T.; Baumgardner, Kody; Zharov, Gabe; Lee, Sarah; Sharifzadeh, Hassan; Shihab, Saeed; Mattinson, Ty; Li, Binxing; Bernstein, Paul S.

    2016-01-01

    A crystal structure of the lutein-binding domain of human StARD3 (StAR-related lipid-transfer protein 3; also known as MLN64) has been refined to 1.74 Å resolution. A previous structure of the same protein determined to 2.2 Å resolution highlighted homology with StARD1 and shared cholesterol-binding character. StARD3 has since been recognized as a carotenoid-binding protein in the primate retina, where its biochemical function of binding lutein with specificity appears to be well suited to recruit this photoprotective molecule. The current and previous structures correspond closely to each other (r.m.s.d. of 0.25 Å), especially in terms of the helix-grip fold constructed around a solvent-filled cavity. Regions of interest were defined with alternate conformations in the current higher-resolution structure, including Arg351 found within the cavity and Ω1, a loop of four residues found just outside the cavity entrance. Models of the complex with lutein generated by rigid-body docking indicate that one of the ionone rings must protrude outside the cavity, and this insight has implications for molecular interactions with transport proteins and enzymes that act on lutein. Interestingly, models with the ∊-ionone ring characteristic of lutein pointing towards the bottom of the cavity were associated with fewer steric clashes, suggesting that steric complementarity and ligand asymmetry may play a role in discriminating lutein from the other ocular carotenoids zeaxanthin and meso-zeaxanthin, which only have β-ionone rings. PMID:27487925

  15. Lutein: a valuable ingredient of fruit and vegetables.

    PubMed

    Calvo, Marta María

    2005-01-01

    Lutein is a human serum carotenoid which is not synthesized by humans and thus must be obtained by the ingestion of food containing it such as fruits and vegetables. Lutein is present in different forms in those foods as all-trans-lutein, cis-lutein, epoxi-lutein, and lutein linked to proteins. It discusses if the intake of lutein or diets supplemented with lutein or diets rich in fruits and vegetables are important in the prevention of diseases like some cancers, cardiovascular diseases, etc., that may be affected by the antioxidant effect of lutein; or in the prevention of age-related macular degeneration and other eye diseases. The concentration of lutein in fruits and vegetables depends on the species. We've included the concentration of lutein in 74 species reported by different authors since 1990. Currently the quantification of lutein is mainly performed by HPLC, but more investigations into a quantification method for lutein, lutein isomers, and epoxi-lutein are necessary. Improvement of lutein extraction methods is important as well. Methods commonly used in the vegetable and fruit industry like heat treatment, storage conditions, etc. can change lutein concentrations; other factors depend on the plant, for instance the variety, the stage of maturity, etc.

  16. Multiple luteinizing hormone receptor (LHR) protein variants, interspecies reactivity of anti-LHR mAb clone 3B5, subcellular localization of LHR in human placenta, pelvic floor and brain, and possible role for LHR in the development of abnormal pregnancy, pelvic floor disorders and Alzheimer's disease.

    PubMed

    Bukovsky, Antonin; Indrapichate, Korakod; Fujiwara, Hiroshi; Cekanova, Maria; Ayala, Maria E; Dominguez, Roberto; Caudle, Michael R; Wimalsena, Jay; Elder, Robert F; Copas, Pleas; Foster, James S; Fernando, Romaine I; Henley, Donald C; Upadhyaya, Nirmala B

    2003-06-03

    Distinct luteinizing hormone receptor (LHR) protein variants exist due to the posttranslational modifications. Besides ovaries, LHR immunoreactivity (LHRI) was also found in other tissues, such as the brain, fallopian tube, endometrium, trophoblast and resident tissue macrophages. The 3B5 mouse monoclonal antibody was raised against purified rat LHR. In rat, porcine and human ovaries, the 3B5 identified six distinct LHR bands migrating at approximately 92, 80, 68, 59, 52 and 48 kDa. Characteristic LHRI was detected in rat, human and porcine corpora lutea. During cellular differentiation, subcellular LHR distribution changed from none to granular cytoplasmic, perinuclear, surface, nuclear and no staining. There were also differences in vascular LHR expression--lack of LHRI in ovarian vessels and strong staining of vessels in other tissues investigated. In normal human term placentae, villous LHRI was associated with blood sinusoids and cytotrophoblast cells, and rarely detected in trophoblastic syncytium. In all abnormal placentae, the LHRI of sinusoids was absent, and syncytium showed either enhanced (immature placental phenotypes) or no LHRI (aged placental phenotype). LHRI in human brain was identified in microglial cells (CD68+ resident macrophages). Protein extracts from human vaginal wall and levator ani muscle and fascia showed strong approximately 92 and 68 kDa species, and LHRI was detected in smooth muscle cells, fibroblasts, resident macrophages and nuclei of skeletal muscle fibers. Our observations indicate that, in contrast to the theory on the role of vascular hormone receptors in preferential pick up of circulating hormones, there is no need to enhance selective pick up rather only prevent LH/CG transport to inappropriate sites. Abnormal placental LHR expression may play a role in the development of abnormal pregnancy. Expression of LHR in the pelvic floor compartments suggests that high LH levels in postmenopausal women may contribute to the pelvic

  17. Multiple luteinizing hormone receptor (LHR) protein variants, interspecies reactivity of anti-LHR mAb clone 3B5, subcellular localization of LHR in human placenta, pelvic floor and brain, and possible role for LHR in the development of abnormal pregnancy, pelvic floor disorders and Alzheimer's disease

    PubMed Central

    Bukovsky, Antonin; Indrapichate, Korakod; Fujiwara, Hiroshi; Cekanova, Maria; Ayala, Maria E; Dominguez, Roberto; Caudle, Michael R; Wimalsena, Jay; Elder, Robert F; Copas, Pleas; Foster, James S; Fernando, Romaine I; Henley, Donald C; Upadhyaya, Nirmala B

    2003-01-01

    Distinct luteinizing hormone receptor (LHR) protein variants exist due to the posttranslational modifications. Besides ovaries, LHR immunoreactivity (LHRI) was also found in other tissues, such as the brain, fallopian tube, endometrium, trophoblast and resident tissue macrophages. The 3B5 mouse monoclonal antibody was raised against purified rat LHR. In rat, porcine and human ovaries, the 3B5 identified six distinct LHR bands migrating at ~92, 80, 68, 59, 52 and 48 kDa. Characteristic LHRI was detected in rat, human and porcine corpora lutea. During cellular differentiation, subcellular LHR distribution changed from none to granular cytoplasmic, perinuclear, surface, nuclear and no staining. There were also differences in vascular LHR expression – lack of LHRI in ovarian vessels and strong staining of vessels in other tissues investigated. In normal human term placentae, villous LHRI was associated with blood sinusoids and cytotrophoblast cells, and rarely detected in trophoblastic syncytium. In all abnormal placentae, the LHRI of sinusoids was absent, and syncytium showed either enhanced (immature placental phenotypes) or no LHRI (aged placental phenotype). LHRI in human brain was identified in microglial cells (CD68+ resident macrophages). Protein extracts from human vaginal wall and levator ani muscle and fascia showed strong ~92 and 68 kDa species, and LHRI was detected in smooth muscle cells, fibroblasts, resident macrophages and nuclei of skeletal muscle fibers. Our observations indicate that, in contrast to the theory on the role of vascular hormone receptors in preferential pick up of circulating hormones, there is no need to enhance selective pick up rather only prevent LH/CG transport to inappropriate sites. Abnormal placental LHR expression may play a role in the development of abnormal pregnancy. Expression of LHR in the pelvic floor compartments suggests that high LH levels in postmenopausal women may contribute to the pelvic floor relaxation and

  18. Lutein extends the lifespan of Drosophila melanogaster.

    PubMed

    Zhang, Zesheng; Han, Shunkai; Wang, Hao; Wang, Tingting

    2014-01-01

    Lutein is one of the major carotenoids in most fruits and vegetables. The effect of lutein on the lifespan of Drosophila melanogaster was investigated. Results revealed that 0.1mg lutein/ml diet could prolong their mean lifespan from 49.0 to 54.6 days. This was consistent with a significant reduction in malonyldialdehyde (MDA) level and increase in antioxidant enzyme activities of the flies fed with lutein-treated diet compared with those fed with basal diet. Paraquat (PQ) and H2O2 treatment tests demonstrated that lutein could prolong the survival time of the flies. Real-time polymerase chain reaction (RT-PCR) analysis indicated the gene expression of superoxide dismutase (SOD; SOD1 and SOD2), and catalase (CAT) in the lutein-treated group was up-regulated relative to that of the control group. It was concluded that the lifespan-prolonging activity of lutein was partially by up-regulation of endogenous antioxidant enzymes.

  19. Induction of Ski Protein Expression upon Luteinization in Rat Granulosa Cells.

    PubMed

    Kim, Hyun; Kim, Dong Hun; Park, Soo Bong; Ko, Yeoung-Gyu; Kim, Sung-Woo; Do, Yoon Jun; Park, Jae-Hong; Yang, Boh-Suk

    2012-05-01

    Ski protein is implicated in proliferation/differentiation in a variety of cells. We had previously reported that Ski protein is present in granulosa cells of atretic follicles, but not in preovulatory follicles, suggesting that Ski has a role in apoptosis of granulosa cells. The alternative fate of granulosa cells other than apoptosis is to differentiate to luteal cells; however, it is unknown whether Ski is expressed and has a role in granulosa cells undergoing luteinization. Thus, the aim of the present study was to locate Ski protein in the rat ovary during luteinizationto predict the possible role of Ski. In order to examine the expression pattern of Ski protein along with the progress of luteinization, follicular growth was induced by administration of equine chorionic gonadtropin to immature female rats, and luteinization was induced by human chorionic gonadtropin treatment to mimic luteinizing hormone (LH) surge. While no Ski-positive granulosa cells were present in preovulatory follicle, Ski protein expression was induced in response to LH surge, and was maintained after the formation of the corpus luteum (CL). Though Ski protein is absent in granulosa cells of preovulatory follicle, its mRNA (c-Ski) was expressed and the level was unchanged even after LH surge. Taken together, these results demonstrated that Ski protein expression is induced in granulosa cells upon luteinization, and suggests that its expression is regulated post-transcriptionally.

  20. Seasonal effects on the endocrine pattern of semi-captive female Asian elephants (Elephas maximus): timing of the anovulatory luteinizing hormone surge determines the length of the estrous cycle.

    PubMed

    Thitaram, C; Brown, J L; Pongsopawijit, P; Chansitthiwet, S; Wongkalasin, W; Daram, P; Roongsri, R; Kalmapijit, A; Mahasawangkul, S; Rojansthien, S; Colenbrander, B; van der Weijden, G C; van Eerdenburg, F J C M

    2008-01-15

    Better breeding strategies for captive Asian elephants in range countries are needed to increase populations; this requires a thorough understanding of their reproductive physiology and factors affecting ovarian activity. Weekly blood samples were collected for 3.9 years from 22 semi-captive female Asian elephants in Thai elephant camps to characterize LH and progestin patterns throughout the estrous cycle. The duration of the estrous cycle was 14.6+/-0.2 weeks (mean+/-S.E.M.; n=71), with follicular and luteal phases of 6.1+/-0.2 and 8.5+/-0.2 weeks, respectively. Season had no significant effect on the overall length of the estrous cycle. However, follicular and luteal phase lengths varied among seasons and were negatively correlated (r=-0.658; P<0.01). During the follicular phase, the interval between the decrease in progestin concentrations to baseline and the anovulatory LH (anLH) surge varied in duration (average 25.9+/-2.0 days, range 7-41, n=23), and was longer in the rainy season (33.4+/-1.8 days, n=10) than in both the winter (22.2+/-4.5 days, n=5; P<0.05) and summer (18.9+/-2.6 days, n=8; P<0.05). By contrast, the interval between the anLH and ovulatory LH (ovLH) surge was more consistent (19.0+/-0.1 days, range 18-20, n=14). Thus, seasonal variation in estrous cycle characteristics were mediated by endocrine events during the early follicular phase, specifically related to timing of the anLH surge. Overall reproductive hormone patterns in Thai camp elephants were not markedly different from those in western zoos. However, this study was the first to more closely examine how timing of the LH surges impacted estrous cycle length in Asian elephants. These findings, and the ability to monitor reproductive hormones in range countries (and potentially in the field), should improve breeding management of captive and semi-wild elephants.

  1. Acute and subacute toxicity assessment of lutein in lutein-deficient mice.

    PubMed

    Nidhi, Bhatiwada; Baskaran, Vallikannan

    2013-10-01

    Dietary lutein consumption is lower than the actual recommended allowances to prevent macular degeneration; thus dietary lutein supplements have been recommended. This study aimed to investigate potential adverse effect of lutein from Tagetes erecta in lutein-deficient (LD) male mice. Preliminary acute toxicity study revealed that the LD50 exceeded the highest dose of 10000 mg/kg BW. In a subacute study, male mice were gavaged with 0, 100, 1000 mg/kg BW/day for a period of 4 wk. Plasma lutein levels increased dose dependently (P < 0.01) after acute and subacute feeding of lutein in LD mice. Compared to the control (peanut oil without lutein) group, no treatment-related toxicologically significant effects of lutein were prominent in clinical observation, ophthalmic examinations, body, and organ weights. Further, no toxicologically significant findings were eminent in hematological, histopathological, and other clinical chemistry parameters. In the oral subacute toxicity study, the no-observed-adverse-effect level (NOAEL) for lutein in LD mice was determined as 1000 mg/kg/day, the highest dose tested. © 2013 Institute of Food Technologists®

  2. Toxicity profile of lutein and lutein ester isolated from marigold flowers (Tagetes erecta).

    PubMed

    Harikumar, Kuzhuvelil Bhaskarannair; Nimita, Chittikappil Venugopal; Preethi, Korengath Chandran; Kuttan, Ramadasan; Shankaranarayana, Madapura Lingappiah; Deshpande, Jayant

    2008-01-01

    Lutein is a carotenoid with antioxidant properties and is commonly present in many fruits, vegetables, and egg yolk. Lutein affords protection against the development of the two common eye diseases of aging: cataract and macular degeneration. As the dietary lutein concentration is much lower compared to the actual requirement to reduce macular degeneration, supplementation of lutein is under consideration. There are very few data on the toxicity of lutein. In the present study, the authors have evaluated the short-term and long-term toxicity profile of lutein and its esterified form isolated from marigold flowers (Tagetes erecta) in young adult male and female Wistar rats. Lutein and its ester form administered orally at doses of 4, 40, and 400 mg/kg body weight for 4 weeks for short-term toxicity study and 13 weeks for a subchronic toxicity study did not produced any mortality, change in body weight, food consumption pattern, organ weight, and other adverse side reactions. Administration of lutein and ester form did not alter the hepatic and renal function, and did not produce any change in the hematological parameters and in lipid profile. Histopathological analysis of the organs supported the nontoxicity of lutein and its ester form.

  3. Regulation by retinoids of luteinizing hormone/chorionic gonadotropin receptor, cholesterol side-chain cleavage cytochrome P-450, 3 beta-hydroxysteroid dehydrogenase/delta (5-4)-isomerase and 17 alpha-hydroxylase/C17-20 lyase cytochrome P-450 messenger ribonucleic acid levels in the K9 mouse Leydig cell line.

    PubMed

    Lefèvre, A; Rogier, E; Astraudo, C; Duquenne, C; Finaz, C

    1994-12-01

    Vitamin A is a potent regulator of testicular function. We have reported that retinol (R) and retinoic acid (RA) induced a down regulation of luteinizing hormone/human chorionic gonadotropin (LH/CG) binding sites in K9 Leydig cells. In the present study we evaluated the effect of R and RA on LH/CG receptors, cholesterol side-chain cleavage cytochrome P-450 (P-450 scc), 17 alpha-hydroxylase/C17-20 lyase (P-450 17 alpha) and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) mRNA levels in K9 mouse Leydig cells. To validate K9 cells as a model for studying Leydig cell steroidogenesis at the molecular level, we first investigated the effect of hCG on mRNA levels of the steroidogenic enzymes. P-450 scc, 3 beta HSD and P-450 17 alpha were expressed constitutively. The addition of 10 ng/ml hCG enhanced mRNA levels for the three genes within 2 h. Maximal accumulation of P-450 scc, P-450 17 alpha and 3 beta HSD mRNA in treated cells represents a 2.5-, 8.5- and 4-fold increase over control values, respectively. P-450 17 alpha expression reached a maximum by 4 h and then declined rapidly to return to control value by 24 h. The pattern of LH/CG receptor mRNAs in K9 cells was very similar to that of MA10 Leydig cells and showed six transcripts of 1.1, 1.6, 1.9, 2.6, 4.2 and 7.0 kb. Treatment of cells with R or RA resulted in a time- and dose-dependent decrease in all six species.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Plasma steroid hormone concentrations and blood flow of the ovarian structures of the female dromedary (Camelus dromedarius) during growth, dominance, spontaneous ovulation, luteinization and regression of the follicular wave.

    PubMed

    Rawy, M S; Derar, R I; El-Sherry, T M; Megahed, G A

    2014-08-01

    The objectives of this study were to investigate the ovarian follicular waves and their corresponding hormonal changes in she-camels and to elucidate blood perfusion of the ovarian structures. Three reproductively sound, non-pregnant female camels were examined daily using B-mode and color Doppler to detect changes in their ovarian structures and blood vasculature for 22 follicular waves. Blood area (BA) and percentage (BA%) were determined for the ovarian structures. Three phases of follicular development, those of growth, maturation, and regression, were observed during each follicular wave. Deviation occurred on Day 6.1±1.08. Estradiol increased from basal levels of 27.4±0.4pg/ml to peak concentrations of 134.4±47.5pg/ml as the follicle reached a diameter of 13.2mm. Peripheral progesterone concentrations remained low (<0.4ng/ml) throughout the follicular waves. The blood flow to the dominant follicles increased gradually with follicular growth. The BA and BA% reached the maximum values of 18.4±11.6mm(2) and 6.04±2.03%, respectively, when the diameter of the dominant follicle was 17.5±3.4mm. The blood flow to the corpus luteum rose markedly after ovulation to reach a maximum BA% and BA at Days 5 and 7, respectively, post ovulation. In conclusion, the follicular wave pattern in dromedaries consists of individually variable periods of growth, maturation and regression. Deviation occurs 6.1±1.08d from emergence. Transrectal color-Doppler sonography is a useful technique for noninvasive evaluation of follicular vascularity in camels during various stages of the follicular wave. It provides additional information to assess the developmental stage and activity of the ovarian structures.

  5. Lutein and cataract: from bench to bedside.

    PubMed

    Manayi, Azadeh; Abdollahi, Mohammad; Raman, Thiagarajan; Nabavi, Seyed Fazel; Habtemariam, Solomon; Daglia, Maria; Nabavi, Seyed Mohammad

    2016-10-01

    Cataract is one of the most important leading causes of blindness in the world. Extensive research showed that oxidative stress may play an important role in the initiation and progression of a cataract and other age-related eye diseases. Extra-generation of reactive oxygen and nitrogen species in the eye tissue has been shown as one of the most important risk factors for cataracts and other age-related eye diseases. With respect to this, it can be hypothesized that dietary antioxidants may be useful in the prevention and/or mitigation of cataract. Lutein is an important xanthophyll which is widely found in different vegetables such as spinach, kale and carrots as well as some other foods such as eggs. Lutein is concentrated in the macula and suppresses the oxidative stress in the eye tissues. A plethora of literature has shown that increased lutein consumption has a close correlation with reduction in the incidence of cataract. Despite this general information, there is a negligible number of review articles considering the beneficial effects of lutein on cataracts and age-related eye diseases. The present review is aimed at discussing the role of oxidative stress in the initiation and progression of a cataract and the possible beneficial effects of lutein in maintaining retinal health and fighting cataract. We also provide a perspective on the chemistry, sources, bioavailability and safety of lutein.

  6. Neuroprotective Effects of Lutein in the Retina

    PubMed Central

    Ozawa, Yoko; Sasaki, Mariko; Takahashi, Noriko; Kamoshita, Mamoru; Miyake, Seiji; Tsubota, Kazuo

    2012-01-01

    Although a large variety of pharmaceutical therapies for treating disease have been developed in recent years, there has been little progress in disease prevention. In particular, the protection of neural tissue is essential, because it is hardly regenerated. The use of nutraceuticals for maintaining the health has been supported by several clinical studies, including cross-sectional and interventional studies for age-related macular disease. However, mechanistic evidence for their effects at the molecular level has been very limited. In this review, we focus on lutein, which is a xanthophyll type of carotenoid. Lutein is not synthesized in mammals, and must be obtained from the diet. It is delivered to the retina, and in humans, it is concentrated in the macula. Here, we describe the neuroprotective effects of lutein and their underlying molecular mechanisms in animal models of vision-threatening diseases, such as innate retinal inflammation, diabetic retinopathy, and light-induced retinal degeneration. In lutein-treated mouse ocular disease models, oxidative stress in the retina is reduced, and its downstream pathological signals are inhibited. Furthermore, degradation of the functional proteins, rhodopsin (a visual substance) and synaptophysin (a synaptic vesicle protein also influenced in other neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease), the depletion of brain-derived neurotrophic factor (BDNF), and DNA damage are prevented by lutein, which preserves visual function. We discuss the possibility of using lutein, an antioxidant, as a neuroprotective treatment for humans. PMID:22211688

  7. Neuroprotective effects of lutein in the retina.

    PubMed

    Ozawa, Yoko; Sasaki, Mariko; Takahashi, Noriko; Kamoshita, Mamoru; Miyake, Seiji; Tsubota, Kazuo

    2012-01-01

    Although a large variety of pharmaceutical therapies for treating disease have been developed in recent years, there has been little progress in disease prevention. In particular, the protection of neural tissue is essential, because it is hardly regenerated. The use of nutraceuticals for maintaining the health has been supported by several clinical studies, including cross-sectional and interventional studies for age-related macular disease. However, mechanistic evidence for their effects at the molecular level has been very limited. In this review, we focus on lutein, which is a xanthophyll type of carotenoid. Lutein is not synthesized in mammals, and must be obtained from the diet. It is delivered to the retina, and in humans, it is concentrated in the macula. Here, we describe the neuroprotective effects of lutein and their underlying molecular mechanisms in animal models of vision-threatening diseases, such as innate retinal inflammation, diabetic retinopathy, and light-induced retinal degeneration. In lutein-treated mouse ocular disease models, oxidative stress in the retina is reduced, and its downstream pathological signals are inhibited. Furthermore, degradation of the functional proteins, rhodopsin (a visual substance) and synaptophysin (a synaptic vesicle protein also influenced in other neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease), the depletion of brain-derived neurotrophic factor (BDNF), and DNA damage are prevented by lutein, which preserves visual function. We discuss the possibility of using lutein, an antioxidant, as a neuroprotective treatment for humans.

  8. Olive oil improves the intestinal absorption and bioavailability of lutein in lutein-deficient mice.

    PubMed

    Nidhi, Bhatiwada; Mamatha, Bangera Sheshappa; Baskaran, V

    2014-02-01

    To investigate the influence of olive (OO), groundnut (GNO), soybean (SBO), sunflower (SFO), rice bran (RBO), corn (CO), palm (PO) oil or mixed micelle (control) on absorption kinetics and bioavailability of lutein in lutein-deficient mice. Additional aim was to correlate the activity of intestinal triacylglycerol lipase with intestinal and plasma lutein levels. After induction of lutein deficiency, mice (n = 165) were divided into eight groups (OO, SFO, GNO, RBO, PO, CO, SBO and control; n = 20/group) and the remaining (n = 5) were used as baseline (0 h). Groups were further divided into four subgroups (n = 5/subgroup) and were intubated with lutein (200 μM) dispersed in different vegetable oils. Plasma and tissue (intestine, liver and eyes), lutein, triglycerides, intestinal triacylglycerol lipases and fatty acid profile of plasma and tissues were measured at different time intervals. The percentage area under the curve value for plasma lutein in OO and GNO was higher by 41.8 and 5.1 %, while it was lower in other groups (18.2-53.3 %), when compared to control. Similarly, the percentage area under the curve for eye lutein in OO and GNO groups was higher by 35.2 and 4.8 %, whereas in other groups it was lower (5.4-69 %) than in control. Results show that olive oil facilitates the lutein absorption more compared to other vegetable oils, which may be due to the difference in fatty acid composition and higher activity of intestinal triacylglycerol lipase. Dietary olive oil rich in oleic acid improves the bioavailability and accumulation of lutein in lutein-deficient mice by modifying the intestinal triacylglycerol lipase activity.

  9. Lutein bioavailability from lutein ester-fortified fermented milk: in vivo and in vitro study.

    PubMed

    Granado-Lorencio, Fernando; Herrero-Barbudo, Carmer; Olmedilla-Alonso, Begoña; Blanco-Navarro, Inmaculada; Pérez-Sacristán, Belén

    2010-02-01

    We assessed the bioavailability of lutein from lutein-fortified fermented milk using in vivo and in vitro approaches. Twenty-four volunteers were randomized to take lutein-fortified fermented milk at two levels of fortification. Single-dose bioavailability study (2x100 ml, ca. 8 or 16 mg of lutein) was performed using a three-point approach (baseline, 3.5 and 6.5 h). Multiple-dose study consisted of consuming one serving/day (ca. 4 or 8 mg/100 ml) for 14 days. Blood samples for biochemical, hematological and lutein analysis were drawn at baseline, Day 7 and Day 14. In vitro bioaccessibility was assessed by a static gastrointestinal digestion model. Lutein content, in vitro ester hydrolysis and micellarization, and lutein concentrations achieved in serum were analyzed by HPLC. In vivo, post-prandial response was higher using the high content fermented milk, but the percentage of absorption was not different according to the dose consumed. Net increments at Day 7 and Day 14 were significantly higher on consuming the high-dose milk as well. In vitro, lutein ester hydrolysis was incomplete regardless of the amount initially present. Free lutein released was higher using the high-dose fermented milk, but the percentage of hydrolysis was similar at both levels of fortification. In the micellar phase, the percentage of free and total lutein was not different according to the dose. Our results support the suitability of the fermented milk as a carrier of lutein esters and an in vivo dose-dependent effect upon regular consumption and suggest the usefulness of in vitro models to provide relevant information to predict in vivo responses. Copyright 2010 Elsevier Inc. All rights reserved.

  10. MULTIPLE STABLE PERIODIC SOLUTIONS IN A MODEL FOR THE HORMONAL REGULATION OF THE MENSTRUAL CYCLE

    EPA Science Inventory

    ABSTRACT

    The pituitary hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the ovarian hormones, estradiol (E2), progesterone (P4), and inhibin (Ih), are five hormones important for the regulation and maintenance of the human menstrual cycle. The...

  11. MULTIPLE STABLE PERIODIC SOLUTIONS IN A MODEL FOR THE HORMONAL REGULATION OF THE MENSTRUAL CYCLE

    EPA Science Inventory

    ABSTRACT

    The pituitary hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the ovarian hormones, estradiol (E2), progesterone (P4), and inhibin (Ih), are five hormones important for the regulation and maintenance of the human menstrual cycle. The...

  12. Effects of long-acting GnRH antagonist, degarelix acetate, on plasma insulin-like peptide 3, testosterone and luteinizing hormone concentrations, and scrotal circumference in male goats.

    PubMed

    Hannan, M A; Kawate, N; Fukami, Y; Weerakoon, W W P N; Büllesbach, E E; Inaba, T; Tamada, H

    2017-01-15

    that of INSL3, the low levels persisted for 8.5 weeks for both hormones, and subsequently the concentrations returned to pretreatment levels. A significant reduction in testicular size was also observed. The quick, long-lasting, and transient suppression of testosterone and INSL3 after a single injection implies a potential application of this antagonist in reversible long-term chemical castration in male goats. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates

    USDA-ARS?s Scientific Manuscript database

    The xanthophyll pigments lutein and zeaxanthin cross the blood-retina barrier to preferentially accumulate in the macular region of the neural retina. There they form macular pigment, protecting the retina from blue light damage and oxidative stress. Lutein and zeaxanthin also accumulate in brain t...

  14. Lutein production from biomass: marigold flowers versus microalgae.

    PubMed

    Lin, Jian-Hao; Lee, Duu-Jong; Chang, Jo-Shu

    2015-05-01

    Microalgae have faster growth rates and more free lutein than marigold flowers, the current source of lutein. However, no commercial lutein production uses microalgae. This review compares lutein content, cultivation, harvesting, cell disruption, and extraction stages of lutein production using marigold flowers and those using microalgae as feedstock. The lutein production rate of microalgae is 3-6 times higher than that of marigold flowers. To produce 1 kg of pure lutein, marigolds need more land and water, but require less nutrients (N, P, K) and less energy than microalgae. Since lutein is tightly bound in microalgae and microalgae are small, cell disruption and subsequent extraction stages consume a considerable amount of energy. Research and development of affordable lutein production from microalgae are discussed.

  15. Concerted transcriptional activation of the low density lipoprotein receptor gene by insulin and luteinizing hormone in cultured porcine granulosa-luteal cells: possible convergence of protein kinase a, phosphatidylinositol 3-kinase, and mitogen-activated protein kinase signaling pathways.

    PubMed

    Sekar, N; Veldhuis, J D

    2001-07-01

    -repressive region in this gene. Non-LH receptor-dependent agonists of protein kinase A (PKA), 8-bromo-cAMP (1 mM), and forskolin (10 microM) with or without insulin/IGF-I costimulation likewise augmented LDL receptor promoter expression with similar strong dependency on the -255 to -139 bp 5'-upstream region. To assess more specific PKA-dependent mediation of LH's contribution to combined hormonal drive, the LDL receptor (-1076 to +11 bp) reporter plasmid was cotransfected with a full-sequence rabbit muscle protein kinase inhibitor (PKI) minigene driven constitutively by a Rous sarcoma virus promoter. Expression of the latter PKA antagonist blocked transcriptional stimulation by LH alone as well as that by LH combined with insulin (or IGF-I) by 70-85% without reducing basal transcriptional activity. Transfection of a mutant inactive (Arg to Gly) Rous sarcoma virus/PKI gene confirmed the specificity of the PKI effect. To investigate the convergent role of the insulin/IGF-I effector pathway mediating bihormonal stimulation of LDL receptor promoter expression, transfected granulosa-luteal cells were pretreated for 30 min with two specific inhibitors of phophatidylinositol 3-kinase, wortmannin (100 nM) and LY 294002 (10 microM), or of mitogen-activated protein kinase kinase, PD 98059 (50 microM), U0126 (10 microM), or the latter's inactive derivative, U0124 (10 microM). Both classes of antagonists impeded the ability of insulin or IGF-I to enhance LH-stimulated LDL receptor promoter expression by 60-80%. In conclusion, the present analyses indicate that LH and insulin (or IGF-I) can up-regulate LDL receptor transcriptional activity supraadditively in porcine granulosa-luteal cells 1) via one or more agonistic cis-acting DNA regions located between -255 and -139 bp 5'- upstream of the transcriptional start site, 2) without abrogating sterol-sensitive repressive of this promoter, and 3) by way of intracellular mechanisms that include the PKA, phophatidylinositol 3-kinase, and mitogen

  16. Induction of Ski protein expression upon luteinization in rat granulosa cells without a change in its mRNA expression.

    PubMed

    Kim, Hyun; Yamanouchi, Keitaro; Matsuwaki, Takashi; Nishihara, Masugi

    2012-01-01

    The Ski protein is implicated in the proliferation/differentiation of a variety of cells. We previously reported that the Ski protein is present in granulosa cells of atretic follicles, but not in preovulatory follicles, suggesting that Ski has a role in apoptosis of granulosa cells. However, granulosa cells cannot only undergo apoptosis but can alternatively differentiate into luteal cells. It is unknown whether Ski is expressed and has a role in granulosa cells undergoing luteinization. Thus, the aim of the present study was to determine the localization of the Ski protein in the rat ovary during luteinization to examine if Ski might play a role in this process. In order to examine the Ski protein expression during the progression of luteinization, follicular growth was induced in immature female rats by administration of equine chorionic gonadotropin, and luteinization was induced by human chorionic gonadotropin treatment to mimic the luteinizing hormone (LH) surge. While no Ski-positive granulosa cells were present in the preovulatory follicle, Ski protein expression was induced in response to the LH surge and was maintained after formation of the corpus luteum (CL). Although the Ski protein is absent from the granulosa cells of the preovulatory follicle, its mRNA (c-ski) was expressed, and the level of c-ski mRNA was unchanged even after the LH surge. The combined results demonstrated that Ski protein expression is induced in granulosa cells upon luteinization, and suggested that its expression is regulated posttranscriptionally.

  17. GATA4 and GATA6 Knockdown During Luteinization Inhibits Progesterone Production and Gonadotropin Responsiveness in the Corpus Luteum of Female Mice.

    PubMed

    Convissar, Scott M; Bennett, Jill; Baumgarten, Sarah C; Lydon, John P; DeMayo, Francesco J; Stocco, Carlos

    2015-12-01

    The surge of luteinizing hormone triggers the genomic reprogramming, cell differentiation, and tissue remodeling of the ovulated follicle, leading to the formation of the corpus luteum. During this process, called luteinization, follicular granulosa cells begin expressing a new set of genes that allow the resulting luteal cells to survive in a vastly different hormonal environment and to produce the extremely high amounts of progesterone (P4) needed to sustain pregnancy. To better understand the molecular mechanisms involved in the regulation of luteal P4 production in vivo, the transcription factors GATA4 and GATA6 were knocked down in the corpus luteum by crossing mice carrying Gata4 and Gata6 floxed genes with mice carrying Cre recombinase fused to the progesterone receptor. This receptor is expressed exclusively in granulosa cells after the luteinizing hormone surge, leading to recombination of floxed genes during follicle luteinization. The findings demonstrated that GATA4 and GATA6 are essential for female fertility, whereas targeting either factor alone causes subfertility. When compared to control mice, serum P4 levels and luteal expression of key steroidogenic genes were significantly lower in conditional knockdown mice. The results also showed that GATA4 and GATA6 are required for the expression of the receptors for prolactin and luteinizing hormone, the main luteotropic hormones in mice. The findings demonstrate that GATA4 and GATA6 are crucial regulators of luteal steroidogenesis and are required for the normal response of luteal cells to luteotropins.

  18. Macular pigment and lutein supplementation in choroideremia.

    PubMed

    Duncan, Jacque L; Aleman, Tomas S; Gardner, Leigh M; De Castro, Elaine; Marks, Daniel A; Emmons, Jessica M; Bieber, Michelle L; Steinberg, Janet D; Bennett, Jean; Stone, Edwin M; MacDonald, Ian M; Cideciyan, Artur V; Maguire, Maureen G; Jacobson, Samuel G

    2002-03-01

    Choroideremia is an incurable X-linked retinal degeneration caused by mutations in the gene encoding Rab escort protein-1. A group of clinically defined and genotyped patients were studied to determine: (1) the degree of rod and cone dysfunction and structural abnormality in the central retina and the level of macular pigment; and (2) the response of macular pigment and foveal vision to a 6 month trial of supplementation with oral lutein (at 20 mg per day). Rod and cone-mediated function was measured with dark-adapted static perimetry; in vivo retinal structure was determined with optical coherence tomography; and macular pigment optical density was measured with heterochromatic flicker photometry. In this cohort of patients (ages 15-65 years), both rod- and cone-mediated central function declined with age as did central retinal thickness. Macular pigment levels did not differ between patients and male control subjects. Supplementation of oral lutein in a subset of patients led to an increase in serum lutein and macular pigment levels; absolute foveal sensitivity did not change. It is concluded that macular pigment density can be augmented by oral intake of lutein in patients with choroideremia. There was no short-term change in the central vision of the patients on the supplement, but long-term influences of lutein supplementation on disease natural history warrant further study.

  19. Assessment of insulin like growth factor-1 and IGF binding protein-3 in healthy Indian girls from Delhi and their correlation with age, pubertal status, obesity and thyroid hormonal status.

    PubMed

    Marwaha, Raman K; Garg, M K; Gupta, Sushil; Khurana, A K; Narang, Archna; Shukla, Manoj; Arora, Preeti; Chadha, Aditi; Nayak, Deb Datta; Manchanda, R K

    2017-06-23

    Population specific data and influence of sub-clinical hypothyroidism on insulin like growth factor-1 (IGF-1) and its binding protein-3 (IGFBP-3) in Indian children is lacking. This study was undertaken to evaluate serum IGF-1 and IGFBP-3 and their correlation with age, gender, pubertal status and thyroid functions. A total of 840 apparently healthy school girls aged 6-18 years, were recruited for the study and underwent assessment of height, weight, body mass index, pubertal status and serum T3, T4, TSH, IGF-1, IGFBP-3 and IGF-1/IGFBP-3 molar ratio. The mean serum levels of IGF-1, IGFBP-3 levels and IGF-1/IGFBP-3 molar ratio were 381.8±240.5 ng/mL, 4.19±2.08 μg/mL and 40.5±37.2%, respectively. The serum IGF-1 and IGF-1/IGFBP-3 molar ratio increased significantly (p<0.0001) at 11 years followed by a steady yet non-significant rise till 16 years of age. A similar pattern was observed for IGFBP-3 showing a steep rise at 12 years and peaking at 16 years. Likewise, serum levels of IGF-1 and molar ratio of IGF-1/IGFBP-3 increased significantly with pubertal maturation from stage 1 to 3 and were higher in overweight girls compared to normal weight and obese girls. The growth factors were no different in girls with or without subclinical hypothyroidism. There was no significant impact of age on IGF-1 and IGFBP-3 in pre-pubertal girls. A sudden marked increase at 11 years followed by a gradual rise in growth factors till 16 years is indicative of pubertal initiation and maturation. Subclinical hypothyroidism did not influence growth factors in girls.

  20. Assessment of insulin like growth factor-1 and IGF binding protein-3 in healthy Indian girls from Delhi and their correlation with age, pubertal status, obesity and thyroid hormonal status.

    PubMed

    Marwaha, Raman K; Garg, M K; Gupta, Sushil; Khurana, A K; Narang, Archna; Shukla, Manoj; Arora, Preeti; Chadha, Aditi; Nayak, Deb Datta; Manchanda, R K

    2017-07-26

    Population specific data and influence of sub-clinical hypothyroidism on insulin like growth factor-1 (IGF-1) and its binding protein-3 (IGFBP-3) in Indian children is lacking. This study was undertaken to evaluate serum IGF-1 and IGFBP-3 and their correlation with age, gender, pubertal status and thyroid functions. A total of 840 apparently healthy school girls aged 6-18 years, were recruited for the study and underwent assessment of height, weight, body mass index, pubertal status and serum T3, T4, TSH, IGF-1, IGFBP-3 and IGF-1/IGFBP-3 molar ratio. The mean serum levels of IGF-1, IGFBP-3 levels and IGF-1/IGFBP-3 molar ratio were 381.8±240.5 ng/mL, 4.19±2.08 μg/mL and 40.5±37.2%, respectively. The serum IGF-1 and IGF-1/IGFBP-3 molar ratio increased significantly (p<0.0001) at 11 years followed by a steady yet non-significant rise till 16 years of age. A similar pattern was observed for IGFBP-3 showing a steep rise at 12 years and peaking at 16 years. Likewise, serum levels of IGF-1 and molar ratio of IGF-1/IGFBP-3 increased significantly with pubertal maturation from stage 1 to 3 and were higher in overweight girls compared to normal weight and obese girls. The growth factors were no different in girls with or without subclinical hypothyroidism. There was no significant impact of age on IGF-1 and IGFBP-3 in pre-pubertal girls. A sudden marked increase at 11 years followed by a gradual rise in growth factors till 16 years is indicative of pubertal initiation and maturation. Subclinical hypothyroidism did not influence growth factors in girls.

  1. Effect of luteinizing hormone overstimulation on equine follicle maturation.

    PubMed

    Schauer, S N; Guillaume, D; Decourt, C; Watson, E D; Briant, C; Donadeu, F X

    2013-02-01

    There is evidence in several species that high circulating LH concentrations can interfere with normal follicle development and ovulation. In the mare, high LH levels after induction of luteolysis with PGF(2α) have been temporally associated with an increased incidence of anovulatory follicles. We hypothesized that a premature increase in LH levels during a follicular wave in mares would disrupt normal follicle maturation leading to ovulatory dysfunction. In experiment 1, all follicles >10 mm were ablated at midestrous cycle in pony mares followed by twice daily administration of equine LH (eLH; 1.6 μg/kg body weight) or saline (vehicle; N = 8 mares per group). When a dominant follicle reached >32 mm, an ovulatory dose of hCG was given. Treatment with eLH had no effects on ovulatory responses or progesterone levels during the posttreatment luteal phase. In experiment 2, after follicle ablation, mares were treated with eLH or vehicle (as above) or were given a single injection of PGF(2α) (N = 7 mares per group), followed by aspiration of a dominant follicle when it reached >32 mm. Administration of eLH induced an increase in circulating LH levels similar to that after PGF(2α) injection. Neither PGF(2α) nor eLH administration had significant effects on follicle growth or total number of follicles in the postablation wave. However, compared with mares treated with vehicle, the preovulatory follicle in the eLH and PGF(2α) groups had lower levels of androstenedione (P = 0.03) and higher levels of insulin-like growth factor I (P = 0.03). Further, levels of prostaglandin E2 in preovulatory follicles tended to be lower in the eLH and PGF(2α) groups (P = 0.06). In conclusion, exposure of developing follicles to high LH in mares did not have apparent effects on ovulation but it induced changes in follicular fluid factor levels which might reflect a disruption in follicle and/or oocyte maturation, indicating the need to further study the implications of using PGF(2α) for the control of fertility in farm animals.

  2. Insulin-like growth factor I (IGF-I) replacement during growth hormone receptor antagonism normalizes serum IGF-binding protein-3 and markers of bone formation in ovariectomized rhesus monkeys.

    PubMed

    Wilson, M E

    2000-04-01

    Previous work from this laboratory has shown that the constant sc infusion of insulin-like growth factor I (IGF-I) to normal pituitary monkeys results in a sustained elevation in circulating concentrations of IGF-binding protein-3 (IGFBP-3), whereas the acute administration of IGF-I to monkeys pretreated with a GH receptor antagonist produces a brief, but significant, elevation in serum IGFBP-3. The present study tested the hypothesis that the constant infusion of IGF-I would normalize serum concentrations of IGFBP-3 in females treated with the GH receptor antagonist. To assess the biological significance of these effects, serum levels of the acid-labile subunit (ALS) and biomarkers for bone formation, osteocalcin, and collagen type I C-terminal propeptide, were also examined. Five female rhesus monkeys were studied over 21 consecutive days involving 7 days of baseline, 7 days of treatment with the GH receptor antagonist (1.0 mg/kg-week, sc), and 7 days of treatment with the GH receptor antagonist supplemented with IGF-I (120 microg/kg x day, sc infusion with osmotic minipump). Within 48 h of the initiation of treatment with the GH receptor antagonist, serum IGF-I and IGFBP-3 were decreased by 40% and 18% from baseline, respectively, and levels continued to decline through the remainder of treatment. However, within 48 h of the initiation of IGF-I administration during GH receptor antagonist treatment, both serum IGF-I and IGFBP-3 were elevated and normalized to baseline values. Serum concentrations of ALS were also decreased by GH antagonism, but levels increased in some (n = 2), but not all, subjects upon administration of IGF-I. Size exclusion ultrafiltration indicated that the amount of IGF-I found in the high molecular mass complex (>100 kDa) decreased significantly during GH antagonism, but was similar during the baseline and IGF-I infusion phases. Finally, treatment with the GH receptor antagonist also significantly reduced serum levels of osteocalcin and

  3. Dose-dependent response of serum lutein and macular pigment optical density to supplementation with lutein esters

    PubMed Central

    Bone, Richard A.; Landrum, John T.

    2010-01-01

    We conducted a study to determine the effect of different doses of a lutein supplement on serum lutein concentration and macular pigment optical density (MPOD). Lutein is one of the major components of human macular pigment. Eighty seven subjects received daily doses of 5, 10, or 20 mg of lutein, or a placebo, over a 140 day period. Serum lutein concentration was determined by HPLC, and MPOD by heterochromatic flicker photometry (HFP). Serum lutein responded positively, except in the placebo group, reaching a plateau that, averaged for each dosage group, was linearly dependent on dose. Likewise MPOD, on average, increased at a rate that varied linearly with dose. For subjects deemed more proficient at HFP, approximately 29% of the variability in MPOD response could be attributed to a linear dependence on the fractional change in serum lutein concentration. We did not detect any significant influence of age on serum lutein uptake or MPOD response. PMID:20599660

  4. Release of Multiple Hormones by a Direct Action of Interleukin-1 on Pituitary Cells

    DTIC Science & Technology

    1987-10-23

    monolayer culture was investigated. Recombinant human IL-I beta stimulated the secretion of adrenocorticotropic hormone, luteinizing hormone, growth ... hormone , and thyroid-stimulating hormone. Prolactin secretion by the monolayers was inhibited by similar doses. These concentrations of IL-I are within

  5. The Impact of Polymeric Nanoencapsulation on the Bioavailability of Lutein

    NASA Astrophysics Data System (ADS)

    Kamil, Alison

    Lutein, a fat-soluble xanthophyll, contributes partially to the health benefits from consuming plant foods. Like all dietary carotenoids, lutein has a low bioavailability. In addition to increasing the intake of lutein-rich foods to enhance lutein status, delivery of lutein in polymeric nanoparticles (NP) presents a novel approach to enhancing lutein bioavailability. The overall research objective of this project was to investigate, in rats, the impact of nanoencapsulation using poly(lactic-co-glycolic acid) (PLGA) on the pharmacokinetics of lutein. We also used an in vitro cell culture approach utilizing human epithelial colorectal adenocarcinoma (Caco-2) cells grown in both conventional (CONV) and permeable support (PS) systems to investigate the impact of PLGA-NP on the absorption of lutein in intestinal cells. In chapter one, we compared the efficacy of lutein absorption in vitro using Caco-2 cells grown in both CONV and PS systems. We further examined the role of the micelle, the physiological vehicle for lutein within the small intestine, on its intestinal absorption in vitro compared to an organic solvent, ethanol, which is safe and consumed by humans. The finding from this study demonstrated that the CONV system displayed a larger efficacy of lutein uptake by Caco-2 cells. Further, in the PS system, micelle components appeared to facilitate more effective intestinal secretion of lutein. These findings suggest that lutein uptake by Caco-2 cells is subject to the influence of culturing system (CONV vs. PS) and delivery vehicle (ethanol vs. micelle). Chapter two examined the impact of PLGA-NP in rats on lutein pharmacokinetics in plasma and distribution in selected tissues as compared to free lutein. We also investigated the effect of nanoencapsulation on the absorption of lutein in intestinal cells compared to a more physiological vehicle, the micelle, using the PS method. In addition, we explored the need of additional micelles for the ultimate absorption of

  6. In vitro scleral lutein distribution by cyclodextrin containing nanoemulsions.

    PubMed

    Liu, Chi-Hsien; Lai, Kuan-Yu; Wu, Wei-Chi; Chen, Yu-Jui; Lee, Wei-Shiou; Hsu, Ching-Yun

    2015-01-01

    Lutein is a macular pigment that contributes to maintaining eye health. The development of lutein-laden nanocarriers for ocular delivery would have the advantages of user friendliness and cost-effectiveness. Nano-scaled vehicles such as cyclodextrin (CD) and nanoemulsion could overcome the barriers caused by the scleral structure. This study focused on the development of hybrid nanocarriers containing nanoemulsion and CD for scleral lutein accumulation. In the presence of the nanoemulsion, CD forms such as βCD and hydroxyethyl (HE) βCD increased the partition of lutein into the porcine sclera. A combination of nanoemulsion and 2% HEβCD enhanced lutein accumulation to 119±6 µg g(-1) h(-1), which was 9.2-fold higher than that with lutein suspension alone. We explored the dose effect of CD in nanoemulsion on scleral lutein and found that the scleral accumulation of lutein was enhanced by increasing the CD content. The novel nanoemulsion had 95% drug-loading efficiency and low cytotoxicity in retinal cells. The CD-modified nanoemulsion not only improved the stability and entrapment efficacy of lutein in the aqueous system but also enhanced scleral lutein accumulation. An increase in the partition coefficient of lutein in porcine sclera when using the CD-modified nanoemulsion was also confirmed.

  7. [Advances in the researches of lutein and alzheimer's disease].

    PubMed

    Xu, Xianrong; Lin, Xiaoming

    2015-05-01

    Lutein, a kind of oxycarotenoid, can pass the blood brain barrier and preferentially accumulate in the human brain, which is the most abundant carotenoid in human brain. Evidence from multiple studies suggested that lutein was closely related to age-related cognitive decline and risk of Alzheimer's disease (AD) in human. Dietary, plasma and brain concentrations of lutein were negatively associated with age-related cognitive decline. Lutein concentrations in plasma and brain were significantly lower in AD patients than those of health control. In human brain, lutein was the sole carotenoid which consistently associated with a range of cognitive function measures. In elderly women, lutein supplement can improve the cognitive function. In this article, we systematically reviewed the literature on the role of lutein in age-related cognitive decline and alzheimer's disease and its possible mechanisms. It may prove some benefit information for the advanced research and prevention of AD.

  8. The effect of different doses of isotretinoin on pituitary hormones.

    PubMed

    Karadag, Ayse Serap; Takci, Zennure; Ertugrul, Derun Taner; Bilgili, Serap Gunes; Balahoroglu, Ragip; Takir, Mumtaz

    2015-01-01

    There are a limited number of studies investigating the side effects and effectiveness of various doses of isotretinoin (ISO). We have previously shown that high-dose ISO affects pituitary hormones. To our knowledge, there is no study in the literature looking into the effects of various doses of ISO on pituitary hormones. We searched pituitary hormones in three groups of different doses in acne patients. We included 105 acne vulgaris patients from two different centers. We divided the patients into three groups; the first group received 0.5-1 mg/kg/day, the second 0.2-0.5 mg/kg/day and the third intermittent 0.5-1 mg/kg/day (only 1 week in 1 month) ISO treatment. Blood samples were collected for biochemistry and hormone analysis, before the treatment and after 3 months. After 3 months of treatment with ISO, luteinizing hormone (LH) (p < 0.001), prolactin (p < 0.001), total testosterone (p < 0.001), adrenocorticotropic hormone (ACTH) (p < 0.001), cortisol (p < 0.001), insulin-like growth factor-binding protein 3 (p < 0.001), insulin-like growth factor 1 (IGF-1) (p = 0.002), growth hormone (GH) (p = 0.002) and free T3 (fT3) (p < 0.001) levels had decreased significantly. Furthermore, we split data into three different groups. Among the patients receiving intermittent-dose ISO, LH, ACTH, IGF-1, GH and fT3 measurements lost significance. Most of the significant measurements observed in the whole group were also significant among the patients receiving high-dose ISO. Additionally, dehydroepiandrosterone sulfate (p = 0.003) levels increased, and free T4 levels decreased significantly. ISO affects pituitary hormones at all of these three doses. The differences in pituitary hormones are more pronounced in high-dose treatment. The weakest effect was observed in the intermittent-dose group. Choosing lower doses of ISO may decrease side effects, however the effectiveness of the treatment may also be diminished. ISO, by affecting the PPARγ/RXR system, may affecting hormone

  9. Lutein: more than just a filter for blue light.

    PubMed

    Kijlstra, Aize; Tian, Yuan; Kelly, Elton R; Berendschot, Tos T J M

    2012-07-01

    Lutein is concentrated in the primate retina, where together with zeaxanthin it forms the macular pigment. Traditionally lutein is characterized by its blue light filtering and anti-oxidant properties. Eliminating lutein from the diet of experimental animals results in early degenerative signs in the retina while patients with an acquired condition of macular pigment loss (Macular Telangiectasia) show serious visual handicap indicating the importance of macular pigment. Whether lutein intake reduces the risk of age related macular degeneration (AMD) or cataract formation is currently a strong matter of debate and abundant research is carried out to unravel the biological properties of the lutein molecule. SR-B1 has recently been identified as a lutein binding protein in the retina and this same receptor plays a role in the selective uptake in the gut. In the blood lutein is transported via high-density lipoproteins (HDL). Genes controlling SR-B1 and HDL levels predispose to AMD which supports the involvement of cholesterol/lutein transport pathways. Apart from beneficial effects of lutein intake on various visual function tests, recent findings show that lutein can affect immune responses and inflammation. Lutein diminishes the expression of various ocular inflammation models including endotoxin induced uveitis, laser induced choroidal neovascularization, streptozotocin induced diabetes and experimental retinal ischemia and reperfusion. In vitro studies show that lutein suppresses NF kappa-B activation as well as the expression of iNOS and COX-2. Since AMD has features of a chronic low-grade systemic inflammatory response, attention to the exact role of lutein in this disease has shifted from a local effect in the eye towards a possible systemic anti-inflammatory function.

  10. Promising interaction between nanoencapsulated lutein with low molecular weight chitosan: characterization and bioavailability of lutein in vitro and in vivo.

    PubMed

    Arunkumar, Ranganathan; Harish Prashanth, Keelara Veerappa; Baskaran, Vallikannan

    2013-11-01

    This study aims to develop water-soluble low molecular weight chitosan (LMWC) nanoencapsules with lutein to improve its bioavailability. Lutein-LMWC nanoencapsules were prepared, characterized and bioavailability was studied in vitro and in vivo with lutein in mixed micelles (control). The particle size ranged between 80-600 nm, which was confirmed by Atomic Force Microscope. The interaction between LMWC and lutein in nanocencapsules by (1)H and (13)C NMR showed the essentiality of water molecules to hold the lutein between LMWC chains of nanoparticle with a reversible weak bond. Bioavailability of lutein (200 μM) in vitro showed that lutein-LMWC nanoencapsules was significantly higher (27.7%) than control. Postprandial lutein level in the plasma (54.5%), liver (53.9%) and eyes (62.8%) of mice fed on nanoencapsulated lutein were higher than the control. LMWC may serve as novel carrier for enhancing the lutein bioavailability and can be suggested as the better dietary compound in food and pharmaceutical applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Lutein and atherosclerosis: Belfast versus Toulouse revisited.

    PubMed

    Howard, A N; Thurnham, D I

    2017-01-01

    In 1995 we reported that mean plasma lutein concentrations in salaried men and women from Toulouse in Southern France were double those in subjects recruited from general practitioner lists in Belfast, Northern Ireland. At the time incidence of coronary heart disease (CHD) in Southern France was among the lowest in Europe and was much higher in Northern Ireland. Plasma lutein is a biomarker of vegetable and fruit intake and evidence suggests that high concentrations are generally associated with better cardiometabolic health. At the time we speculated like others that role of the carotenoids may well have been to prevent oxidation of lipid in the lipoproteins and so reduce the uptake of oxidised lipid by macrophages and its deposition within the intimal layers of the major arteries as plaque. It is now widely accepted that CHD is an inflammatory disease and that macrophages within plaque together with tissue damage contribute to this inflammation. Stimulated macrophages release cytokines to activate the immune system both locally and systemically. Precursor complement proteins in the blood are activated to assist immune cells in phagocytosis and cell repair. Individuals with a history of arteriosclerosis display significantly higher concentrations of complement factors C3 and C3a than subjects without such a history. Metabolism of C3 via the alternate complement pathway can give rise to the membrane attack complex (MAC) which creates a hole or pore in pathogens or host cells, killing the cell. Recent studies in patients with early age related macular disease (AMD) who also exhibit similar elevated concentrations of complement proteins in their blood, showed supplementation with lutein progressively decreased the amount of the MAC and other complement factors in the blood. Lutein was used in the supplementation experiments because it is an important constituent of macular pigment. Thus the healthier cardiometabolic features displayed by the people in Toulouse may

  12. Lutein, a carotenoid, suppresses osteoclastic bone resorption and stimulates bone formation in cultures.

    PubMed

    Tominari, Tsukasa; Matsumoto, Chiho; Watanabe, Kenta; Hirata, Michiko; Grundler, Florian M W; Inada, Masaki; Miyaura, Chisato

    2017-02-01

    Lutein, a member of the xanthophyll family of carotenoids, suppressed IL-1-induced osteoclast differentiation and bone resorption. The survival of mature osteoclasts was also suppressed by lutein in cultures. When lutein was added to the cultures of osteoblasts, lutein enhanced the formation of mineralized bone nodules by elevating BMP2 expression and inhibiting sclerostin expression. Lutein may be beneficial for bone health.

  13. Breeding success and lutein availability in great tit ( Parus major)

    NASA Astrophysics Data System (ADS)

    Sillanpää, Saila; Salminen, Juha-Pekka; Eeva, Tapio

    2009-11-01

    The relationship among temporal variation in the availability of carotenoid-rich food, tissue carotenoid levels and breeding success are poorly known. We studied how diet quality and quantity affect the carotenoid profile and fledging success of great tit ( Parus major) nestlings along a pollution gradient. We found declining seasonal trend in lutein concentration of caterpillars, which may be the explanation for the declining trend in nestlings' lutein concentration of plasma with season, despite the increase in caterpillar biomass. This may be because the biomass of most lutein-rich caterpillars (autumnal moths) decreased and less lutein-rich caterpillars (sawflies) increased during the breeding season. The temporal difference in occurrence of different caterpillar species means that peak lutein availability does not coincide with peak caterpillar abundance. However the positive association between total larval biomass and the number of great tit fledglings may suggest that fledging success depends more on total caterpillar availability than on lutein concentration of caterpillars.

  14. Analytical validation of an ultraviolet-visible procedure for determining lutein concentration and application to lutein-loaded nanoparticles.

    PubMed

    Silva, Jéssica Thaís do Prado; Silva, Anderson Clayton da; Geiss, Julia Maria Tonin; de Araújo, Pedro Henrique Hermes; Becker, Daniela; Bracht, Lívia; Leimann, Fernanda Vitória; Bona, Evandro; Guerra, Gustavo Petri; Gonçalves, Odinei Hess

    2017-09-01

    Lutein is a carotenoid presenting known anti-inflammatory and antioxidant properties. Lutein-rich diets have been associated with neurological improvement as well as reduction of the risk of vision loss due to Age-Related Macular Degeneration (AMD). Micro and nanoencapsulation have demonstrated to be effective techniques in protecting lutein against degradation and also in improving its bioavailability. However, actual lutein concentration inside the capsules and encapsulation efficiency are key parameters that must be precisely known when designing in vitro and in vivo tests. In this work an analytical procedure was validated for the determination of the actual lutein content in zein nanoparticles using ultraviolet-visible spectroscopy. Method validation followed the International Conference on Harmonisation (ICH) guidelines which evaluate linearity, detection limit, quantification limit, accuracy and precision. The validated methodology was applied to characterize lutein-loaded nanoparticles. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. The resonance Raman excitation profile of lutein

    NASA Astrophysics Data System (ADS)

    Hoskins, L. C.

    The resonance Raman excitation profiles for the ν 1, ν 2 and ν 3 vibrations of lutein in acetone, toluene and carbon disulfide solvents have been measured. The results are interpreted in terms of a three-mode vibrational theory which includes both homogeneous and inhomogeneous broadening effects. Excellent agreement between calculated and observed excitation profiles and visible spectra was found in acetone and toluene, but the results in carbon disulfide indicate a possible breakdown in the three-mode model. The major broadening mechanism is homogeneous, with about a 25% contribution from inhomogeneous broadening.

  16. Potential influence of hormones in the development of slipped capital femoral epiphysis: a preliminary study.

    PubMed

    Papavasiliou, Kyriakos A; Kirkos, John M; Kapetanos, George A; Pournaras, John

    2007-01-01

    The potential influence of hormonal imbalance on the development of slipped capital femoral epiphysis was assessed through a prospective clinical study. The serum levels of T3, T4, thyroid-stimulating hormone, testosterone, estradiol, dehydroepiandrosterone-sulfate, follicle-stimulating hormone, luteinizing hormone, human growth hormone, adrenal cortex hormone and cortisol were evaluated in seven boys and seven girls. Forty-three out of 154 hormonal determinations (27.9%) were abnormal. The results showed increased incidence of pathological values mainly in the levels of follicle-stimulating-hormone, luteinizing-hormone and testosterone. No patient had clinical findings of endocrinopathy. A (possibly) temporary hormonal disorder may play a potentially significant role in the development of slipped capital femoral epiphysis.

  17. Novel Lutein Loaded Lipid Nanoparticles on Porcine Corneal Distribution

    PubMed Central

    Liu, Chi-Hsien; Chiu, Hao-Che; Wu, Wei-Chi; Sahoo, Soubhagya Laxmi; Hsu, Ching-Yun

    2014-01-01

    Topical delivery has the advantages including being user friendly and cost effective. Development of topical delivery carriers for lutein is becoming an important issue for the ocular drug delivery. Quantification of the partition coefficient of drug in the ocular tissue is the first step for the evaluation of delivery efficacy. The objectives of this study were to evaluate the effects of lipid nanoparticles and cyclodextrin (CD) on the corneal lutein accumulation and to measure the partition coefficients in the porcine cornea. Lipid nanoparticles combined with 2% HPβCD could enhance lutein accumulation up to 209.2 ± 18 (μg/g) which is 4.9-fold higher than that of the nanoparticles. CD combined nanoparticles have 68% of drug loading efficiency and lower cytotoxicity in the bovine cornea cells. From the confocal images, this improvement is due to the increased partitioning of lutein to the corneal epithelium by CD in the lipid nanoparticles. The novel lipid nanoparticles could not only improve the stability and entrapment efficacy of lutein but also enhance the lutein accumulation and partition in the cornea. Additionally the corneal accumulation of lutein was further enhanced by increasing the lutein payload in the vehicles. PMID:25101172

  18. Antioxidant effect of lutein towards phospholipid hydroperoxidation in human erythrocytes.

    PubMed

    Nakagawa, Kiyotaka; Kiko, Takehiro; Hatade, Keijiro; Sookwong, Phumon; Arai, Hiroyuki; Miyazawa, Teruo

    2009-11-01

    Peroxidised phospholipid-mediated cytotoxity is involved in the pathophysiology of many diseases; for example, phospholipid hydroperoxides (PLOOH) are abnormally increased in erythrocytes of dementia patients. Dietary carotenoids (especially xanthophylls, polar carotenoids such as lutein) have gained attention as potent inhibitors against erythrocyte phospholipid hydroperoxidation, thereby making them plausible candidates for preventing diseases (i.e. dementia). To evaluate these points, we investigated whether orally administered lutein is distributed to human erythrocytes, and inhibits erythrocyte PLOOH formation. Six healthy subjects took one capsule of food-grade lutein (9.67 mg lutein per capsule) once per d for 4 weeks. Before and during the supplementation period, carotenoids and PLOOH in erythrocytes and plasma were determined by our developed HPLC technique. The administered lutein was incorporated into human erythrocytes, and erythrocyte PLOOH level decreased after the ingestion for 2 and 4 weeks. The antioxidative effect of lutein was confirmed on erythrocyte membranes, but not in plasma. These results suggest that lutein has the potential to act as an important antioxidant molecule in erythrocytes, and it thereby may contribute to the prevention of dementia. Therefore future biological and clinical studies will be required to evaluate the efficacy as well as safety of lutein in models of dementia with a realistic prospect of its use in human therapy.

  19. Bioconversion of lutein to form aroma compounds by Pantoea dispersa.

    PubMed

    Zhao, Yue; Zhong, Gui Fang; Yang, Xue Peng; Hu, Xian Mei; Mao, Duo Bin; Ma, Yu Ping

    2015-08-01

    To investigate the conversion of lutein, a carotenoid, to aroma compounds by Pantoea dispersa Y08, a lutein-degrading bacterium isolated from marigold flower residue. Bioconversion conditions, including substrate concentration, applied co-solvent and reaction time, were optimized. A maximum biodegradation yield of 80 % for lutein at 10 g/l was achieved. The intermediate, 3-hydroxy-β-ionone, and final β-ionone products were revealed by GC-MS. A bioconversion pathway of lutein is proposed to involve cleavage at the 9-10 double bond position, followed by de-hydroxylation at the 3-hydroxy position. This is the first report of the ability of a bacterium, P. dispersa, to sequentially convert lutein to 3-hydroxy-β-ionone and then β-ionone.

  20. Is Lutein a Physiologically Important Ligand for Transthyretin in Humans?

    SciTech Connect

    Chen, Liwei

    2003-01-01

    Lutein and zeaxanthin are the only carotenoids accumulated in the macula of the human retina and are known as the macular pigments (MP). These pigments account for the yellow color of the macula and appear to play an important role in protecting against age-related macular degeneration (AMD). The uptake of lutein and zeaxanthin in human eyes is remarkably specific. It is likely that specific transport or binding proteins are involved. The objective is to determine whether transthyretin (TTR) is a transport protein in human plasma and could thus deliver lutein from the blood to the retina. In this study, they used a biosynthetic 13C-lutein tracer and gas chromatography-combustion interfaced-isotope ratio mass spectrometry (GCC-IRMS) to gain the requisite sensitivity to detect the minute amounts of lutein expected as a physiological ligand for human transthyretin. The biosynthetic 13C-labeled lutein tracer was purified from algae. Healthy women (n = 4) each ingested 1 mg of 13C-labeled lutein daily for 3 days and a blood sample was collected 24 hours after the final dose. Plasma TTR was isolated by retinol-binding protein (RBP)-sepharose affinity chromatography and extracted with chloroform. The 13C/12C ratio in the TTR extract was measured by GCC-IRMS. There was no 13C-lutein enrichment in the pure TTR extract. This result indicated that lutein is not associated with TTR in human plasma after ingestion in physiological amounts. Some hydrophobic compounds with yellow color may bind to human TTR in the plasma. However, this association needs to be further proved by showing specificity. The study provides a new approach for carotenoid-binding protein studies using a stable isotope tracer method combined with the high precision of GCC-IRMS. The mechanism of selective transport, uptake, and accumulation of lutein in human macula remain to be determined.

  1. Bioavailability of lutein from a lutein-enriched egg-yolk beverage and its dried re-suspended versions.

    PubMed

    Bunger, Meike; Quataert, Miriam; Kamps, Lisette; Versloot, Pieter; Hulshof, Paul J M; Togtema, Arnoud; van Amerongen, Aart; Mensink, Marco

    2014-11-01

    Drying a fresh lutein-enriched egg-yolk beverage would extend its shelf life, however, functional properties should not be affected. It was investigated whether consumption of a dried beverage containing lutein-enriched egg-yolk significantly increases serum lutein. One-hundred healthy young subjects participated in this 6-weeks randomized controlled study. Subjects consumed either a "plain" control beverage (n = 26), a fresh lutein-enriched egg-yolk beverage (n = 25), a dried version of this beverage (n = 25), or a beverage composed of the dried individual components of the drink (n = 24). The fresh and both dried versions of the lutein-enriched egg-yolk beverage were able to increase serum lutein levels after 6 weeks of consumption (lutein change: -38 ± 47 nmol/L, +304 ± 113 nmol/L, +148 ± 79 nmol/L and +178 ± 83 nmol/L for control, fresh, dried and combined dried group respectively; p < 0.001). No significant change in serum cholesterol level was seen in the beverages containing lutein-enriched egg-yolk compared to the control drink.

  2. Changes in Macular Pigment Optical Density and Serum Lutein Concentration in Japanese Subjects Taking Two Different Lutein Supplements

    PubMed Central

    Okazaki, Shigetoshi; Gellermann, Werner; Bernstein, Paul S.

    2015-01-01

    Purpose To investigate macular pigment optical density (MPOD) and serum concentration changes of lutein in Japanese subjects participating in a clinical trial in which two formulations of lutein and zeaxanthin supplements with different physiochemical properties are used. Methods Thirty-six healthy volunteers were recruited into this prospective, randomized, parallel-group, double-masked comparative study at a single institute. Two products were used, FloraGLO® (Kemin Japan) and XanMax® (Katra Phytochem). The lutein particle size and zeaxanthin concentrations differed between the formulations. The subjects consumed one of the two supplements for a duration of up to 6 months. MPOD levels were measured by resonance Raman spectrometry at baseline and once a month until the end of the study. Serum lutein concentration was measured at baseline, month 3, and month 6. The subjects were also tested for contrast sensitivity, glare sensitivity, visual acuity, and in addition had a focal electroretinogram measured. Results The mean serum lutein concentrations increased significantly after the first three months, but the mean MPOD levels in either supplement group did not show any statistically significant increase. A detailed analysis, however, revealed three response patterns in both groups for the increase of MPOD levels and serum lutein concentration, i.e. “retinal responders”, who had an increase of both MPOD levels and serum lutein concentrations (n = 13), “retinal non-responders”, who had only increased serum concentrations and no change in MPOD levels (n = 20), and “retinal and serum non-responders”, who had neither MPOD level nor plasma concentration increases (n = 3). The subjects with low MPOD levels at baseline appeared to show increased MPOD levels at the 6 month time point upon lutein supplementation (r = -0.4090, p = 0.0133). Glare sensitivity improved in retinal responders in both supplement groups, while there were no remarkable changes in

  3. Changes in Macular Pigment Optical Density and Serum Lutein Concentration in Japanese Subjects Taking Two Different Lutein Supplements.

    PubMed

    Obana, Akira; Tanito, Masaki; Gohto, Yuko; Okazaki, Shigetoshi; Gellermann, Werner; Bernstein, Paul S

    2015-01-01

    To investigate macular pigment optical density (MPOD) and serum concentration changes of lutein in Japanese subjects participating in a clinical trial in which two formulations of lutein and zeaxanthin supplements with different physiochemical properties are used. Thirty-six healthy volunteers were recruited into this prospective, randomized, parallel-group, double-masked comparative study at a single institute. Two products were used, FloraGLO® (Kemin Japan) and XanMax® (Katra Phytochem). The lutein particle size and zeaxanthin concentrations differed between the formulations. The subjects consumed one of the two supplements for a duration of up to 6 months. MPOD levels were measured by resonance Raman spectrometry at baseline and once a month until the end of the study. Serum lutein concentration was measured at baseline, month 3, and month 6. The subjects were also tested for contrast sensitivity, glare sensitivity, visual acuity, and in addition had a focal electroretinogram measured. The mean serum lutein concentrations increased significantly after the first three months, but the mean MPOD levels in either supplement group did not show any statistically significant increase. A detailed analysis, however, revealed three response patterns in both groups for the increase of MPOD levels and serum lutein concentration, i.e. "retinal responders", who had an increase of both MPOD levels and serum lutein concentrations (n = 13), "retinal non-responders", who had only increased serum concentrations and no change in MPOD levels (n = 20), and "retinal and serum non-responders", who had neither MPOD level nor plasma concentration increases (n = 3). The subjects with low MPOD levels at baseline appeared to show increased MPOD levels at the 6 month time point upon lutein supplementation (r = -0.4090, p = 0.0133). Glare sensitivity improved in retinal responders in both supplement groups, while there were no remarkable changes in contrast sensitivity. No statistically

  4. Lutein Protects RGC-5 Cells Against Hypoxia and Oxidative Stress

    PubMed Central

    Li, Suk-Yee; Lo, Amy C. Y.

    2010-01-01

    Retinal ischemia and oxidative stress lead to neuronal death in many ocular pathologies. Recently, we found that lutein, an oxy-carotenoid, protected the inner retina from ischemia/reperfusion injury. However, it is uncertain whether lutein directly protects retinal ganglion cells (RGCs). Here, an in vitro model of hypoxia and oxidative stress was used to further investigate the neuroprotective role of lutein in RGCs. Cobalt chloride (CoCl2) and hydrogen peroxide (H2O2) were added to a transformed RGC cell line, RGC-5, to induce chemical hypoxia and oxidative stress, respectively. Either lutein or vehicle was added to cultured cells. A higher cell count was observed in the lutein-treated cells compared with the vehicle-treated cells. Our data from this in vitro model revealed that lutein might protect RGC-5 cells from damage when exposed to either CoCl2-induced chemical hypoxia or H2O2-induced oxidative stress. These results suggest that lutein may play a role as a neuroprotectant. PMID:20559505

  5. Effects of a lutein supplement on the plasma lutein concentration and macular pigment in patients with central serous chorioretinopathy.

    PubMed

    Sawa, Miki; Gomi, Fumi; Hara, Chikako; Nishida, Kohji

    2014-07-29

    To investigate the effects of lutein supplementation on plasma lutein concentrations and the macular pigment optical density (MPOD) in central serous chorioretinopathy (CSC). In this double-masked placebo-controlled study, 20 patients received lutein 20 mg/d and 19 received placebo. The plasma lutein concentration and MPOD using autofluorescence spectrometry (density unit, DU) were measured at baseline and 1 and 4 months. The mean plasma lutein concentrations and MPOD values in the lutein and control groups, respectively, were 91.5 and 78.2 ng/mL and 0.444 and 0.437 DU at baseline; 204.9 and 79.3 ng/mL and 0.460 and 0.442 DU at 1 month; and 228.0 and 78.4 ng/mL and 0.441 and 0.421 DU at 4 months. The plasma concentration in the lutein group was significantly higher than in controls at 1 and 4 months (P < 0.0001 for both comparisons); however, the MPOD values did not differ significantly between groups at 1 (P = 0.479) or 4 months (P = 0.883). In patients with a plasma lutein concentration below the mean level in 20 age-matched healthy subjects (mean 105.3 ng/mL; n = 13 in lutein group, n = 15 in control group), the control MPOD values significantly (P = 0.0430) decreased at 4 months (mean baseline, 0.437 DU; 4 months, 0.404 DU). The MPOD in the lutein group remained at the baseline level (mean baseline, 0.426 DU; 4 months, 0.438 DU) (P = 0.6542). The MPOD did not increase in patients with CSC with short-term lutein supplementation; however, among patients with low plasma lutein, supplemental lutein prevented a decline in MPOD that was observed in control subjects (www.umin.ac.jp/ctr number, UMIN000005849). Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  6. Microalgae as a source of lutein: chemistry, biosynthesis, and carotenogenesis.

    PubMed

    Sun, Zheng; Li, Tao; Zhou, Zhi-gang; Jiang, Yue

    2016-01-01

    Microalgae represent a sustainable source of natural products, and over 15,000 novel compounds originated from algal biomass have been identified. This chapter focuses on algae-derived lutein, a group of high-value products. Lutein belongs to carotenoids which have extensive applications in feed, food, nutraceutical, and pharmaceutical industries. The production of carotenoids has been one of the most successful activities in microalgal biotechnology. This chapter gives a mini review of microalgae-based lutein, where emphasis is placed on the biosynthetic pathway and the regulation of carotenogenesis.

  7. Lutein and lutein esters in whole grain flours made from 75 genotypes of 5 triticum species grown at multiple sites.

    PubMed

    Ziegler, Jochen U; Wahl, Sabine; Würschum, Tobias; Longin, C Friedrich H; Carle, Reinhold; Schweiggert, Ralf M

    2015-05-27

    Concentrations of lutein and lutein esters were determined in an ample collection of 75 wheat genotypes comprising bread wheat (Triticum aestivum L.), durum (Triticum durum Desf.), spelt (Triticum spelta L.), emmer (Triticum dicoccum Schrank), and einkorn (Triticum monococcum L.) grown in five different environments. Einkorn genotypes showed the highest total amounts of lutein (4.5-7.8 μg/g dry matter), followed by durum (2.0-4.6 μg/g), spelt (0.9-2.0 μg/g), emmer (0.8-1.9 μg/g), and bread wheat (0.7-2.0 μg/g). Due to the observed highly significant genetic variance and high heritability, lutein contents of wheat genotypes may be increased by future plant breeding. Detailed HPLC-DAD-APCI(±)-MS(n) data allowing the identification of six lutein monoesters and nine diesters are presented. Linoleic, palmitic, and oleic acids were the most abundant fatty acids in both the lutein esters and total free lipid fractions. Lutein esters were virtually absent in the tetraploid durum and emmer species, whereas their concentrations considerably differed among the genotypes belonging to the other species.

  8. Male hormonal contraceptives.

    PubMed

    Amory, J K

    2006-06-01

    Efforts are underway to develop additional forms of contraception for men. The most promising approach to male contraceptive development involves the administration of exogenous testosterone (T). When administered to a man, T functions as a contraceptive by suppressing the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary, thereby depriving the testes of the signals required for spermatogenesis. After 2-3 months of treatment, low levels of these gonadotropins lead to markedly decreased sperm counts and effective contraception in a majority of men. Hormonal contraception with exogenous T has proven to be free from serious adverse effects and is well tolerated by men. In addition, sperm counts uniformly normalize when the exogenous T is discontinued. Thus, male hormonal is safe, effective and reversible; however, spermatogenesis is not suppressed to zero in all men, meaning that some diminished potential for fertility persists. Because of this recent studies have combined T with progestogens and/or gonadotropin-releasing antagonists to further suppress pituitary gonadotropins and optimize contraceptive efficacy. Current combinations of T and progestogens completely suppress spermatogenesis without severe side effects in 80-90% of men, with significant suppression in the remainder of individuals. Recent trials with newer, long-acting forms of injectable T, which can be administered every 8 weeks, combined with progestogens, administered either orally or by long-acting implant, have yielded promising results and may soon result in the marketing of a safe, reversible and effective hormonal contraceptive for men.

  9. Targeting luteinizing hormone-releasing hormone: A potential therapeutics to treat gynecological and other cancers.

    PubMed

    Ghanghoria, Raksha; Kesharwani, Prashant; Tekade, Rakesh K; Jain, Narendra K

    2016-11-10

    Cancer is a prime healthcare problem that is significantly responsible for universal mortality. Despite distinguished advancements in medical field, chemotherapy is still the mainstay for the treatment of cancers. During chemotherapy, approximately 90% of the administered dose goes to normal tissues, with mere 2-5% precisely reaching the cancerous tissues. Subsequently, the resultant side effects and associated complications lead to dose reduction or even discontinuance of the therapy. Tumor directed therapy therefore, represents a fascinating approach to augment the therapeutic potential of anticancer bioactives as well as overcomes its side effects. The selective overexpression of LHRH receptors on human tumors compared to normal tissues makes them a suitable marker for diagnostics, molecular probes and targeted therapeutics. These understanding enabled the rational to conjugate LHRH with various cytotoxic drugs (doxorubicin, DOX; camptothecin etc.), cytotoxic genes [small interfering RNA (siRNA), micro RNA (miRNA)], as well as therapeutic nanocarriers (nanoparticles, liposomes or dendrimers) to facilitate their tumor specific delivery. LHRH conjugation enhances their delivery via LHRH receptor mediated endocytosis. Numerous cytotoxic analogs of LHRH were developed over the past two decades to target various types of cancers. The potency of LHRH compound were reported to be as high as 5,00-10,00 folds compared to parent molecules. The objective of this review article is to discuss reports on various LHRH analogs with special emphasis on their prospective application in the medical field. The article also focuses on the attributes that must be taken into account while designing a LHRH therapeutics with special account to the biochemistry and applications of these conjugates. The record on various cytotoxic analogs of LHRH are also discussed. It is anticipated that the knowledge of therapeutic and toxicological aspects of LHRH compounds will facilitate the development of a more systematic approach to the targeted delivery of cytotoxic agents using peptides.

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

    SciTech Connect

    Kile, J.P.

    1986-01-01

    The hypothesis was tested that GnRH acts to release LH by increasing calcium uptake by gonadotroph which in turn stimulates calcium-calmodulin activity and results in LH release from bovine pituitary cells as it does in the rat. Pituitary glands of calves (4-10 months of age) were enzymatically dispersed (0.2% collagenase) and grown for 5 days to confluency in multiwell plates (3 x 10/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.

  11. Catecholestrogens and release of anterior pituitary gland hormones. I. Luteinizing hormone.

    PubMed

    Rodriguez-Sierra, J F; Blake, C A

    1982-02-01

    We investigated the effects of peripheral administration of 17 beta-estradiol (E2), estrone (E1), and the catecholestrogens, 2-hydroxyestradiol (2-OHE2) and 2-hydroxyestrone (2-OHE1), on anterior pituitary gland LH release in the prepuberal rat. Steroids in oil were injected sc into 25-day-old female and 35- to 40-day-old male rats. The injection of E2, E1, or 2-OHE2 caused a surge in serum LH levels in female rats 48 h later, during the after hours. Only E1 induced a LH surge 24 h after injection. The positive effects of 2-OHE2 in the females were only observed if a massive dose was administered, the steroid was injected on 2 consecutive days, or E2 or progesterone was given to 2-OHE2-primed rats. The 2-OHE1 was totally ineffective in causing a serum LH surge under a variety of experimental protocols. In male rats, the injection of any one of the four steroids decreased serum LH levels. Even the injection of E2 or 2-OHE2 for 2 days or the injection of E2 in 2-OHE2-primed rats failed to elevate the serum LH concentration in male rats. The results suggest that 2-OHE2 and E1 could play a role in the preovulatory release of LH in the female; 2-OHE2 and 2-OHE1 could play a role in the negative feedback control of LH release in the male.

  12. Hormones in Synergy: Regulation of the Pituitary Gonadotropin Genes

    PubMed Central

    Thackray, Varykina G.; Mellon, Pamela L.; Coss, Djurdjica

    2009-01-01

    The precise interplay of hormonal influences that governs gonadotropin hormone production by the pituitary includes endocrine, paracrine and autocrine actions of hypothalamic gonadotropin-releasing hormone (GnRH), activin and steroids. However, most studies of hormonal regulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the pituitary gonadotrope have been limited to analyses of the isolated actions of individual hormones. LHβ and FSHβ subunits have distinct patterns of expression during the menstrual/estrous cycle as a result of the integration of activin, GnRH, and steroid hormone action. In this review, we focus on studies that delineate the interplay among these hormones in the regulation of LHβ and FSHβ gene expression in gonadotrope cells and discuss how signaling cross-talk contributes to differential expression. We also discuss how recent technological advances will help identify additional factors involved in the differential hormonal regulation of LH and FSH. PMID:19747958

  13. Hormone levels

    MedlinePlus

    Blood or urine tests can determine the levels of various hormones in the body. This includes reproductive hormones, thyroid hormones, adrenal hormones, pituitary hormones, and many others. For more information, see: ...

  14. Lutein protects against ischemia/reperfusion injury in rat kidneys.

    PubMed

    Liu, Zhen-Guo; Qi, Zong-Cai; Liu, Wei-Liang; Wang, Wei-Zhi

    2015-03-01

    Ischemia‑reperfusion (I/R) injury has a major impact on renal dysfunction during transplantation. The present study investigated the role of lutein against I/R injury‑induced oxidative stress in rat kidneys. Biochemical analysis and oxidative stress parameters demonstrated that lutein protected the rat kidney significantly from I/R injury. Pretreatment with lutein significantly increased the total antioxidant capacity with a concomitant decline in the total oxidant status. Rats with I/R injury showed a significant increase in oxidative stress. The results revealed significant increases in the levels of lipid peroxidation and protein carbonyl content with concomitant decreases in enzymic and non‑enzymic antioxidants. The activity of these enzymes was reversed and demonstrated a significant increase following lutein pre‑treatment compared with the rats subjected to I/R injury alone. Furthermore, lutein protected the renal tissue from I/R injury by maintaining normal kidney architecture and led to a reduction in the levels of the renal markers urea and creatinine in the serum. These results demonstrated clear evidence that lutein offered a significant protective effect against I/R injury by enhancing antioxidant defense mechanisms.

  15. Lutein Inhibits the Migration of Retinal Pigment Epithelial Cells via Cytosolic and Mitochondrial Akt Pathways (Lutein Inhibits RPE Cells Migration)

    PubMed Central

    Su, Ching-Chieh; Chan, Chi-Ming; Chen, Han-Min; Wu, Chia-Chun; Hsiao, Chien-Yu; Lee, Pei-Lan; Lin, Victor Chia-Hsiang; Hung, Chi-Feng

    2014-01-01

    During the course of proliferative vitreoretinopathy (PVR), the retinal pigment epithelium (RPE) cells will de-differentiate, proliferate, and migrate onto the surfaces of the sensory retina. Several studies have shown that platelet-derived growth factor (PDGF) can induce migration of RPE cells via an Akt-related pathway. In this study, the effect of lutein on PDGF-BB-induced RPE cells migration was examined using transwell migration assays and Western blot analyses. We found that both phosphorylation of Akt and mitochondrial translocation of Akt in RPE cells induced by PDGF-BB stimulation were suppressed by lutein. Furthermore, the increased migration observed in RPE cells with overexpressed mitochondrial Akt could also be suppressed by lutein. Our results demonstrate that lutein can inhibit PDGF-BB induced RPE cells migration through the inhibition of both cytoplasmic and mitochondrial Akt activation. PMID:25110866

  16. [Is lutein supplementation inefficacious? Consideration of the scientific opinion on lutein and maintenance of vision and legal classification].

    PubMed

    Jakobs, S; Skarupinski, P

    2013-02-01

    The aim of this article is the detailed consideration of the scientific opinion on the substantiation of health claims related to lutein and maintenance of vision, which was published by European Food Safety Authority (EFSA). The findings regarding the efficacy of lutein are important for the legal product classification. Thus, the second part of this paper will focus on products containing lutein regarding the demarcation between foodstuffs and drugs. These products are often used in ophthalmology and therefore the assessment of the legal product classification is also important to know for the attending ophthalmologists. Summing up, it is stated that the national and European law for placing products containing lutein on the market will be harmonised for reasons of clarity, transparency and legal certainty but also providing tighter admission requirements for these kinds of products.

  17. Dietary lutein absorption from marigold extract is rapid in BALB/c mice.

    PubMed

    Park, J S; Chew, B P; Wong, T S

    1998-10-01

    Even though lutein can stimulate immunity and decrease cancer growth, no systematic studies are available on the uptake of lutein in mice. We studied the uptake of lutein in 8-wk-old female BALB/c mice fed a diet containing 0, 0.05, 0.1, 0.2 or 0.4% lutein. Mice were killed on d 0, 3, 7, 14, 21 and 28 (n = 6/period), and blood, spleen and liver were collected. Food intake and body, liver and spleen weights did not differ among treatment groups. Lutein + zeaxanthin were not detectable in the plasma, liver and spleen of unsupplemented mice. Mice fed lutein showed very rapid lutein + zeaxanthin absorption. On d 3, concentrations of plasma lutein + zeaxanthin had rapidly increased (P < 0.05) in lutein-fed mice and no further increases were observed. Plasma lutein + zeaxanthin concentrations did not differ among lutein-fed mice by d 7 (2.58 +/- 0.2 micromol/L). Even though maximal uptake of plasma lutein + zeaxanthin was observed by d 3, uptake of lutein + zeaxanthin by the liver and especially by the spleen generally continued to increase (P < 0.05) through d 28 to reach concentrations of 0.11 +/- 0.001 (spleen) and 0.71 +/- 0. 0002 (liver) nmol/g. Therefore, dietary lutein is readily absorbed into the plasma and taken up by liver and spleen of mice. Plasma lutein + zeaxanthin concentrations were higher than in human studies; however, mice were fed lutein at a level several hundredfold greater than in humans. The liver is a major storage organ for lutein + zeaxanthin in mice. Uptake of lutein + zeaxanthin by the spleen suggests a role for lutein in modulating immunity.

  18. Composition of Lutein Ester Regioisomers in Marigold Flower, Dietary Supplement, and Herbal Tea.

    PubMed

    Abdel-Aal, El-Sayed M; Rabalski, Iwona

    2015-11-11

    Characterization of lutein and its esters in a health product is necessary for its efficacy. In the current study lutein ester regioisomers were quantified and identified in several dietary supplements and herbal teas in comparison with marigold flower, the commercial source of lutein. The products were extracted with three solvents and separated on a C30 column. The separated esters were identified/confirmed with LC-MS in APCI+ve mode with the use of synthetic lutein esters. The total content of lutein esters substantially varied among marigold flowers (167-5752 μg/g), supplements (88,000-110,700 μg/g), and herbal teas (12.4-91.3 μg/g). Lutein supplement had a lutein profile similar to that of marigold flower, whereas herbal tea showed an extremely different profile. Lutein dipalmitate was the dominant compound in supplements and marigold flowers followed by lutein 3'-O-myristate-3-O-palmitate and lutein 3'-O-palmitate-3-O-myristate. Lutein was the major compound in marigold herbal tea with small amounts of lutein mono- and diesters. Differences in the concentration and composition of lutein compounds among marigold products could indicate distinct product quality and lutein bioavailability.

  19. A FEEDBACK MODEL FOR TESTICULAR-PITUITARY AXIS HORMONE KINETICS AND THEIR EFFECTS ON THE REGULATION OF THE PROSTATE IN ADULT MALE RATS

    EPA Science Inventory

    The testicular-hypothalamic-pituitary axis regulates male reproductive system functions. A model describing the kinetics and dynamics of testosterone (T), dihydrotestosterone (DHT) and luteinizing hormone (LH) was developed based on a model by Barton and Anderson (1997). The mode...

  20. A FEEDBACK MODEL FOR TESTICULAR-PITUITARY AXIS HORMONE KINETICS AND THEIR EFFECTS ON THE REGULATION OF THE PROSTATE IN ADULT MALE RATS

    EPA Science Inventory

    The testicular-hypothalamic-pituitary axis regulates male reproductive system functions. A model describing the kinetics and dynamics of testosterone (T), dihydrotestosterone (DHT) and luteinizing hormone (LH) was developed based on a model by Barton and Anderson (1997). The mode...