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Sample records for pulsatile luteinizing hormone

  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. 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

  3. 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.

  4. 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.

  5. 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 ...

  6. Does cortisol acting via the type II glucocorticoid receptor mediate suppression of pulsatile luteinizing hormone secretion in response to psychosocial stress?

    PubMed

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

    2007-04-01

    This study assessed the importance of cortisol in mediating inhibition of pulsatile LH secretion in sheep exposed to a psychosocial stress. First, we developed an acute psychosocial stress model that involves sequential layering of novel stressors over 3-4 h. This layered-stress paradigm robustly activated the hypothalamic-pituitary-adrenal axis and unambiguously inhibited pulsatile LH secretion. We next used this paradigm to test the hypothesis that cortisol, acting via the type II glucocorticoid receptor (GR), mediates stress-induced suppression of pulsatile LH secretion. Our approach was to determine whether an antagonist of the type II GR (RU486) reverses inhibition of LH pulsatility in response to the layered stress. We used two animal models to assess different aspects of LH pulse regulation. With the first model (ovariectomized ewe), LH pulse characteristics could vary as a function of both altered GnRH pulses and pituitary responsiveness to GnRH. In this case, antagonism of the type II GR did not prevent stress-induced inhibition of pulsatile LH secretion. With the second model (pituitary-clamped ovariectomized ewe), pulsatile GnRH input to the pituitary was fixed to enable assessment of stress effects specifically at the pituitary level. In this case, the layered stress inhibited pituitary responsiveness to GnRH and antagonism of the type II GR reversed the effect. Collectively, these findings indicate acute psychosocial stress inhibits pulsatile LH secretion, at least in part, by reducing pituitary responsiveness to GnRH. Cortisol, acting via the type II GR, is an obligatory mediator of this effect. However, under conditions in which GnRH input to the pituitary is not clamped, antagonism of the type II GR does not prevent stress-induced inhibition of LH pulsatility, implicating an additional pathway of suppression that is independent of cortisol acting via this receptor.

  7. 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... 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...

  8. 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...

  9. 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... 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...

  10. 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...

  11. 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... 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...

  12. 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.

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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

  18. 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

  19. Nonlinear analysis and prediction of pulsatile hormone secretion

    NASA Astrophysics Data System (ADS)

    Prank, Klaus; Kloppstech, Mirko; Nowlan, Steven J.; Harms, Heio M.; Brabant, Georg; Hesch, Rolf-Dieter; Sejnowski, Terrence J.

    1996-06-01

    Pulsatile hormone secretion is observed in almost every hormonal system. The frequency of episodic hormone release ranges from approximately 10 to 100 pulses in 24 hours. This temporal mode of secretion is an important feature of intercellular information transfer in addition to a dose-response dependent regulation. It has been demonstrated in a number of experiments that changes in the temporal pattern of pulsatile hormone secretion specifically regulate cellular and organ function and structure. Recent evidence links osteoporosis, a disease characterized by loss of bone mass and structure, to changes in the dynamics of pulsatile parathyroid hormone (PTH) secretion. In our study we applied nonlinear and linear time series prediction to characterize the secretory dynamics of PTH in both healthy human subjects and patients with osteoporosis. Osteoporotic patients appear to lack periods of high predictability found in normal humans. In contrast to patients with osteoporosis patients with hyperparathyroidism, a condition which despite sometimes reduced bone mass has a preserved bone architecture, show periods of high predictability of PTH secretion. Using stochastic surrogate data sets which match certain statistical properties of the original time series significant nonlinear determinism could be found for the PTH time series of a group of healthy subjects. Using classical nonlinear analytical techniques we could demonstrate that the irregular pattern of pulsatile PTH secretion in healthy men exhibits characteristics of deterministic chaos. Pulsatile secretion of PTH in healthy subjects seems to be a first example of nonlinear determinism in an apparently irregular hormonal rhythm in human physiology.

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

    SciTech Connect

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

    1989-08-01

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

  1. Nonlinear analysis and prediction of pulsatile hormone secretion

    SciTech Connect

    Prank, K. |; Kloppstech, M.; Nowlan, S.J.; Harms, H.M.; Brabant, G.; Hesch, R.; Sejnowski, T.J.

    1996-06-01

    Pulsatile hormone secretion is observed in almost every hormonal system. The frequency of episodic hormone release ranges from approximately 10 to 100 pulses in 24 hours. This temporal mode of secretion is an important feature of intercellular information transfer in addition to a dose-response dependent regulation. It has been demonstrated in a number of experiments that changes in the temporal pattern of pulsatile hormone secretion specifically regulate cellular and organ function and structure. Recent evidence links osteoporosis, a disease characterized by loss of bone mass and structure, to changes in the dynamics of pulsatile parathyroid hormone (PTH) secretion. In our study we applied nonlinear and linear time series prediction to characterize the secretory dynamics of PTH in both healthy human subjects and patients with osteoporosis. Osteoporotic patients appear to lack periods of high predictability found in normal humans. In contrast to patients with osteoporosis patients with hyperparathyroidism, a condition which despite sometimes reduced bone mass has a preserved bone architecture, show periods of high predictability of PTH secretion. Using stochastic surrogate data sets which match certain statistical properties of the original time series significant nonlinear determinism could be found for the PTH time series of a group of healthy subjects. Using classical nonlinear analytical techniques we could demonstrate that the irregular pattern of pulsatile PTH secretion in healthy men exhibits characteristics of deterministic chaos. Pulsatile secretion of PTH in healthy subjects seems to be a first example of nonlinear determinism in an apparently irregular hormonal rhythm in human physiology. {copyright} {ital 1996 American Institute of Physics.}

  2. Nutrient Sensing Overrides Somatostatin and Growth Hormone-Releasing Hormone to Control Pulsatile Growth Hormone Release.

    PubMed

    Steyn, F J

    2015-07-01

    Pharmacological studies reveal that interactions between hypothalamic inhibitory somatostatin and stimulatory growth hormone-releasing hormone (GHRH) govern pulsatile GH release. However, in vivo analysis of somatostatin and GHRH release into the pituitary portal vasculature and peripheral GH output demonstrates that the withdrawal of somatostatin or the appearance of GHRH into pituitary portal blood does not reliably dictate GH release. Consequently, additional intermediates acting at the level of the hypothalamus and within the anterior pituitary gland are likely to contribute to the release of GH, entraining GH secretory patterns to meet physiological demand. The identification and validation of the actions of such intermediates is particularly important, given that the pattern of GH release defines several of the physiological actions of GH. This review highlights the actions of neuropeptide Y in regulating GH release. It is acknowledged that pulsatile GH release may not occur selectively in response to hypothalamic control of pituitary function. As such, interactions between somatotroph networks, the median eminence and pituitary microvasculature and blood flow, and the emerging role of tanycytes and pericytes as critical regulators of pulsatility are considered. It is argued that collective interactions between the hypothalamus, the median eminence and pituitary vasculature, and structural components within the pituitary gland dictate somatotroph function and thereby pulsatile GH release. These interactions may override hypothalamic somatostatin and GHRH-mediated GH release, and modify pulsatile GH release relative to the peripheral glucose supply, and thereby physiological demand.

  3. Biomathematical Modeling of Pulsatile Hormone Secretion: A Historical Perspective

    PubMed Central

    Evans, William S.; Farhy, Leon S.; Johnson, Michael L.

    2009-01-01

    Shortly after the recognition of the profound physiological significance of the pulsatile nature of hormone secretion, computer-based modeling techniques were introduced for the identification and characterization of such pulses. Whereas these earlier approaches defined perturbations in hormone concentration-time series, deconvolution procedures were subsequently employed to separate such pulses into their secretion event and clearance components. Stochastic differential equation modeling was also used to define basal and pulsatile hormone secretion. To assess the regulation of individual components within a hormone network, a method that quantitated approximate entropy within hormone concentration-times series was described. To define relationships within coupled hormone systems, methods including cross-correlation and cross-approximate entropy were utilized. To address some of the inherent limitations of these methods, modeling techniques with which to appraise the strength of feedback signaling between and among hormone-secreting components of a network have been developed. Techniques such as dynamic modeling have been utilized to reconstruct dose–response interactions between hormones within coupled systems. A logical extension of these advances will require the development of mathematical methods with which to approximate endocrine networks exhibiting multiple feedback interactions and subsequently reconstruct their parameters based on experimental data for the purpose of testing regulatory hypotheses and estimating alterations in hormone release control mechanisms. PMID:19216934

  4. 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...

  5. 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

  6. 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.

  7. 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

  8. Motivations and Methods for Analyzing Pulsatile Hormone Secretion

    PubMed Central

    Veldhuis, Johannes D.; Keenan, Daniel M.; Pincus, Steven M.

    2008-01-01

    Endocrine glands communicate with remote target cells via a mixture of continuous and intermittent signal exchange. Continuous signaling allows slowly varying control, whereas intermittency permits large rapid adjustments. The control systems that mediate such homeostatic corrections operate in a species-, gender-, age-, and context-selective fashion. Significant progress has been made in understanding mechanisms of adaptive interglandular signaling in vivo. Principal goals are to understand the physiological origins, significance, and mechanisms of pulsatile hormone secretion. Key analytical issues are: 1) to quantify the number, size, shape, and uniformity of pulses, nonpulsatile (basal) secretion, and elimination kinetics; 2) to evaluate regulation of the axis as a whole; and 3) to reconstruct dose-response interactions without disrupting hormone connections. This review will focus on the motivations driving and the methodologies used for such analyses. PMID:18940916

  9. 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.

  10. Pulsatile Release of Parathyroid Hormone from an Implantable Delivery System

    PubMed Central

    Liu, Xiaohua; Pettway, Glenda J.; McCauley, Laurie K.; Ma, Peter X.

    2007-01-01

    Intermittent (pulsatile) administration of parathyroid hormone (PTH) is known to improve bone micro-architecture, mineral density and strength. Therefore, daily injection of PTH has been clinically used for the treatment of osteoporosis. However, this regimen of administration is not convenient and is not a favorable choice of patients. In this study, an implantable delivery system has been developed to achieve pulsatile release of PTH. A well-defined cylindrical device was first fabricated with a biodegradable polymer, poly(lactic acid) (PLLA), using a reverse solid free form fabrication technique. Three-component polyanhydrides composed of sebacic acid, 1,3-bis(p-carboxyphenoxy) propane and poly(ethylene glycol) were synthesized and used as isolation layers. The polyanhydride isolation layers and PTH-loaded alginate layers were then stacked alternately within the delivery device. The gap between the stacked PTH-releasing core and the device frame was filled with PLLA to seal. Multi-pulse PTH release was achieved using the implantable device. The lag time between two adjacent pulses were modulated by the composition and the film thickness of the polyanhydride. The released PTH was demonstrated to be biologically active using an in vitro assay. Timed sequential release of multiple drugs has also been demonstrated. The implantable device holds promise for both systemic and local therapies. PMID:17576005

  11. 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.

  12. 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.

  13. 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 ...

  14. 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.

  15. 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

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

    PubMed

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

    2001-12-01

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

  17. 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.

  18. 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.

  19. 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...

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Adrenocorticotropic hormone versus pulsatile dexamethasone in the treatment of infantile epilepsy syndromes.

    PubMed

    Haberlandt, Edda; Weger, Christine; Sigl, Sara Baumgartner; Rauchenzauner, Markus; Scholl-Bürgi, Sabine; Rostásy, Kevin; Karall, Daniela

    2010-01-01

    For treatment of intractable epilepsies, there are no data comparing conventional adrenocorticotropic hormone and pulsatile corticoid therapy with dexamethasone. A retrospective comparison of efficacy was therefore conducted for both forms of application. Between 1989 and 2001, a series of 11 children with West syndrome and 3 with Lennox-Gastaut syndrome were treated with adrenocorticotropic hormone (group 1); between 2003 and 2006, 7 children with West syndrome, 5 with electrical status epilepticus during slow sleep, and 2 with Lennox-Gastaut syndrome were treated with pulsatile corticoid therapy (group 2). In group 1 (n = 14), 9/11 West syndrome patients became seizure free, but none with Lennox-Gastaut syndrome (0/3). In group 2 (n = 14), 4/7 West syndrome patients became seizure-free, 1/2 with Lennox-Gastaut syndrome exhibited seizure-frequency reduction, and 2/5 patients with electrical status epilepticus during slow-wave sleep exhibited significant improvement according to electroencephalograms. In West syndrome, pulsatile corticoid therapy was an effective alternative treatment to adrenocorticotropic hormone, whereas in Lennox-Gastaut syndrome in general steroids did not lead to a significant seizure reduction. In electrical status epilepticus during slow-wave sleep, treatment with pulsatile corticoid therapy seems to be effective and should be investigated in a larger group of patients.

  6. 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.

  7. 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.

  8. 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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

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

    NASA Astrophysics Data System (ADS)

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

    1995-03-01

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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Comparison of pulsatile vs. continuous administration of human placental growth hormone in female C57BL/6J mice.

    PubMed

    Liao, Shutan; Vickers, Mark H; Evans, Angharad; Stanley, Joanna L; Baker, Philip N; Perry, Jo K

    2016-10-01

    Exogenous growth hormone has different actions depending on the method of administration. However, the effects of different modes of administration of the placental variant of growth hormone on growth, body composition and glucose metabolism have not been investigated. In this study, we examined the effect of pulsatile vs. continuous administration of recombinant variant of growth hormone in a normal mouse model. Female C57BL/6J mice were randomized to receive vehicle or variant of growth hormone (2 or 5 mg/kg per day) by daily subcutaneous injection (pulsatile) or osmotic pump for 6 days. Pulsatile treatment with 2 and 5 mg/kg per day significantly increased body weight. There was also an increase in liver, kidney and spleen weight via pulsatile treatment, whereas continuous treatment did not affect body weight or organ size. Pulsatile treatment with 5 mg/kg per day significantly increased fasting plasma insulin concentration, whereas with continuous treatment, fasting insulin concentration was not significantly different from the vehicle-treated control. However, a dose-dependent increase in fasting insulin concentration and decrease in insulin sensitivity, as assessed by HOMA, was observed with both modes of treatment. At 5 mg/kg per day, hepatic growth hormone receptor expression was increased compared to vehicle-treated animals, by both modes of administration. Pulsatile variant of growth hormone did not alter the plasma insulin-like growth factor-1 concentration, whereas a slight decrease was observed with continuous variant of growth hormone treatment. Neither pulsatile nor continuous treatment affected hepatic insulin-like growth factor-1 mRNA expression. Our findings suggest that pulsatile variant of growth hormone treatment was more effective in stimulating growth but caused marked hyperinsulinemia in mice.

  18. 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

  19. Synchronous activation of gonadotropin-releasing hormone gene transcription and secretion by pulsatile kisspeptin stimulation

    PubMed Central

    Choe, Han Kyoung; Kim, Hee-Dae; Park, Sung Ho; Lee, Han-Woong; Park, Jae-Yong; Seong, Jae Young; Lightman, Stafford L.; Son, Gi Hoon; Kim, Kyungjin

    2013-01-01

    Pulsatile release of hypothalamic gonadotropin-releasing hormone (GnRH) is essential for pituitary gonadotrope function. Although the importance of pulsatile GnRH secretion has been recognized for several decades, the mechanisms underlying GnRH pulse generation in hypothalamic neural networks remain elusive. Here, we demonstrate the ultradian rhythm of GnRH gene transcription in single GnRH neurons using cultured hypothalamic slices prepared from transgenic mice expressing a GnRH promoter-driven destabilized luciferase reporter. Although GnRH promoter activity in each GnRH neuron exhibited an ultradian pattern of oscillations with a period of ∼10 h, GnRH neuronal cultures exhibited partially synchronized bursts of GnRH transcriptional activity at ∼2-h intervals. Surprisingly, pulsatile administration of kisspeptin, a potent GnRH secretagogue, evoked dramatic synchronous activation of GnRH gene transcription with robust stimulation of pulsatile GnRH secretion. We also addressed the issue of hierarchical interaction between the circadian and ultradian rhythms by using Bmal1-deficient mice with defective circadian clocks. The circadian molecular oscillator barely affected basal ultradian oscillation of GnRH transcription but was heavily involved in kisspeptin-evoked responses of GnRH neurons. In conclusion, we have clearly shown synchronous bursts of GnRH gene transcription in the hypothalamic GnRH neuronal population in association with episodic neurohormone secretion, thereby providing insight into GnRH pulse generation. PMID:23509283

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. Developmental changes in hypothalamic Kiss1 expression during activation of the pulsatile release of luteinising hormone in maturing ewe lambs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Onset of puberty is characterized by a marked increase in the frequency of release of gonadotrophin-releasing hormone (GnRH) and luteinizing hormone (LH). The KISS1 gene plays a critical role in pubertal development and its product, kisspeptin, stimulates GnRH and LH release. In the study reported h...

  10. 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

  11. 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.

  12. Atrazine inhibits pulsatile gonadotropin-releasing hormone (GnRH) release without altering GnRH messenger RNA or protein levels in the female rat.

    PubMed

    Foradori, Chad D; Zimmerman, Arthur D; Hinds, Laura R; Zuloaga, Kristen L; Breckenridge, Charles B; Handa, Robert J

    2013-01-01

    Atrazine (ATR) is a commonly used pre-emergence/early postemergence herbicide. Previous work has shown that exposure to high doses of ATR in rats results in blunting of the hormone-induced luteinizing hormone (LH) surge and inhibition of pulsatile LH release without significantly reducing pituitary sensitivity to a gonadotropin-releasing hormone (GnRH) agonist. Accompanying the reduction in the LH surge was an attenuation of GnRH neuronal activation. These findings suggest that ATR exposure may be acting to inhibit GnRH release. In this study, we examined GnRH directly to determine the effect of high doses of ATR on GnRH pulsatile release, gene expression, and peptide levels in the female rat. Ovariectomized adult female Wistar rats were treated with ATR (200 mg/kg) or vehicle for 4 days via gavage. Following the final treatment, GnRH release was measured from ex vivo hypothalamic explants for 3 h. In another experiment, animals were administered either vehicle or ATR (50, 100, or 200 mg/kg) daily for 4 days. Following treatment, in situ hybridization was performed to examine total GnRH mRNA and the primary GnRH heterogeneous nuclear RNA transcript. Finally, GnRH immunoreactivity and total peptide levels were measured in hypothalamic tissue of treated animals. ATR treatment resulted in no changes to GnRH gene expression, peptide levels, or immunoreactivity but a reduction in GnRH pulse frequency and an increased pulse amplitude. These findings suggest that ATR acts to inhibit the secretory dynamics of GnRH pulses without interfering with GnRH mRNA and protein synthesis.

  13. Biological Time Series Analysis Using a Context Free Language: Applicability to Pulsatile Hormone Data

    PubMed Central

    Dean, Dennis A.; Adler, Gail K.; Nguyen, David P.; Klerman, Elizabeth B.

    2014-01-01

    We present a novel approach for analyzing biological time-series data using a context-free language (CFL) representation that allows the extraction and quantification of important features from the time-series. This representation results in Hierarchically AdaPtive (HAP) analysis, a suite of multiple complementary techniques that enable rapid analysis of data and does not require the user to set parameters. HAP analysis generates hierarchically organized parameter distributions that allow multi-scale components of the time-series to be quantified and includes a data analysis pipeline that applies recursive analyses to generate hierarchically organized results that extend traditional outcome measures such as pharmacokinetics and inter-pulse interval. Pulsicons, a novel text-based time-series representation also derived from the CFL approach, are introduced as an objective qualitative comparison nomenclature. We apply HAP to the analysis of 24 hours of frequently sampled pulsatile cortisol hormone data, which has known analysis challenges, from 14 healthy women. HAP analysis generated results in seconds and produced dozens of figures for each participant. The results quantify the observed qualitative features of cortisol data as a series of pulse clusters, each consisting of one or more embedded pulses, and identify two ultradian phenotypes in this dataset. HAP analysis is designed to be robust to individual differences and to missing data and may be applied to other pulsatile hormones. Future work can extend HAP analysis to other time-series data types, including oscillatory and other periodic physiological signals. PMID:25184442

  14. Reduced pulsatile growth hormone secretion in children after therapy for acute lymphoblastic leukemia

    SciTech Connect

    Blatt, J.; Bercu, B.B.; Gillin, J.C.; Mendelson, W.B.; Poplack, D.G.

    1984-02-01

    Basal growth hormone levels were measured every 20 minutes over 24 hours in eight long-term survivors of acute lymphoblastic leukemia and in 13 age- and pubertal stage-matched normal children. Among the patients, the median total basal growth hormone output (AUC) was 43 units, compared with 341 units in the normal control group (P less than 0.001). In the patients, mean pulse amplitude (6.9 ng/ml) and frequency (4.6) over 24 hours also were reduced, compared with the control values (32 ng/ml and 8.5, P less than 0.001 and P less than 0.05, respectively). In addition, normal children secreted more GH at night (median AUC 280) than during the day (113, P less than 0.001). However, this diurnal pattern was absent in three of the patients studied. These data suggest that perturbations of spontaneous pulsatile GH secretion are common after standard therapy for ALL and may be a sensitive means of detecting therapy-related neuroendocrine damage. Blunting of spontaneous pulsatile GH secretion may contribute to the abnormalities in growth seen in children with ALL.

  15. Biological time series analysis using a context free language: applicability to pulsatile hormone data.

    PubMed

    Dean, Dennis A; Adler, Gail K; Nguyen, David P; Klerman, Elizabeth B

    2014-01-01

    We present a novel approach for analyzing biological time-series data using a context-free language (CFL) representation that allows the extraction and quantification of important features from the time-series. This representation results in Hierarchically AdaPtive (HAP) analysis, a suite of multiple complementary techniques that enable rapid analysis of data and does not require the user to set parameters. HAP analysis generates hierarchically organized parameter distributions that allow multi-scale components of the time-series to be quantified and includes a data analysis pipeline that applies recursive analyses to generate hierarchically organized results that extend traditional outcome measures such as pharmacokinetics and inter-pulse interval. Pulsicons, a novel text-based time-series representation also derived from the CFL approach, are introduced as an objective qualitative comparison nomenclature. We apply HAP to the analysis of 24 hours of frequently sampled pulsatile cortisol hormone data, which has known analysis challenges, from 14 healthy women. HAP analysis generated results in seconds and produced dozens of figures for each participant. The results quantify the observed qualitative features of cortisol data as a series of pulse clusters, each consisting of one or more embedded pulses, and identify two ultradian phenotypes in this dataset. HAP analysis is designed to be robust to individual differences and to missing data and may be applied to other pulsatile hormones. Future work can extend HAP analysis to other time-series data types, including oscillatory and other periodic physiological signals.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  2. 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.

  3. 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.

  4. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  6. 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.

  7. 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.

  8. 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

  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. 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.

  13. 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.

  14. 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.

  15. 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.

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

    SciTech Connect

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

    1989-08-01

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

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Enhanced basal and disorderly growth hormone secretion distinguish acromegalic from normal pulsatile growth hormone release.

    PubMed Central

    Hartman, M L; Pincus, S M; Johnson, M L; Matthews, D H; Faunt, L M; Vance, M L; Thorner, M O; Veldhuis, J D

    1994-01-01

    Pulses of growth hormone (GH) release in acromegaly may arise from hypothalamic regulation or from random events intrinsic to adenomatous tissue. To distinguish between these possibilities, serum GH concentrations were measured at 5-min intervals for 24 h in acromegalic men and women with active (n = 19) and inactive (n = 9) disease and in normal young adults in the fed (n = 20) and fasted (n = 16) states. Daily GH secretion rates, calculated by deconvolution analysis, were greater in patients with active acromegaly than in fed (P < 0.05) but not fasted normal subjects. Significant basal (nonpulsatile) GH secretion was present in virtually all active acromegalics but not those in remission or in fed and fasted normal subjects. A recently introduced scale- and model-independent statistic, approximate entropy (ApEn), was used to test for regularity (orderliness) in the GH data. All but one acromegalic had ApEn values greater than the absolute range in normal subjects, indicating reduced orderliness of GH release; ApEn distinguished acromegalic from normal GH secretion (fed, P < 10(-12); fasted, P < 10(-7)) with high sensitivity (95%) and specificity (100%). Acromegalics in remission had ApEn scores larger than those of normal subjects (P < 0.0001) but smaller than those of active acromegalics (P < 0.001). The coefficient of variation of successive incremental changes in GH concentrations was significantly lower in acromegalics than in normal subjects (P < 0.001). Fourier analysis in acromegalics revealed reduced fractional amplitudes compared to normal subjects (P < 0.05). We conclude that GH secretion in acromegaly is highly irregular with disorderly release accompanying significant basal secretion. Images PMID:8083369

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. Leptin is a potent stimulator of spontaneous pulsatile growth hormone (GH) secretion and the GH response to GH-releasing hormone.

    PubMed

    Tannenbaum, G S; Gurd, W; Lapointe, M

    1998-09-01

    Pulsatile GH secretion is exquisitely sensitive to perturbations in nutritional status, but the underlying mechanisms are largely unknown. Leptin, a recently discovered adipose cell hormone, is thought to be a sensor of energy stores and to regulate body mass, appetite, and metabolism at the level of the brain. Receptors for leptin are abundantly expressed in hypothalamic nuclei known to be involved in GH regulation, suggesting that leptin may serve as an important hormonal signal to the GH neuroendocrine axis in normal animals. To test this hypothesis, we examined the effects of intracerebroventricular infusion of recombinant murine leptin, at a dose of 1.2 microg/day for 7 days, on both spontaneous and GH-releasing hormone (GHRH)-stimulated GH secretion in free-moving adult male rats. Concomitant with suppressive effects on food intake, body weight, and basal plasma insulin-like growth factor I, insulin, and glucose concentrations, central infusion of leptin resulted in a 2- to 3-fold augmentation of GH pulse amplitude, 5-fold higher GH nadir levels, and a 2- to 3-fold increase in the integrated area under the 6-h GH response curve compared with those in vehicle-infused controls (P < 0.001). The intracerebroventricular infusion of leptin also produced a 3- to 4-fold increase in GHRH-induced GH release at GH trough times (P < 0.01). These studies demonstrate a potent stimulatory action of leptin on both spontaneous pulsatile GH secretion and the GH response to GHRH. The results suggest that the GH-releasing activity of leptin is mediated, at least in part, by an inhibition of hypothalamic somatostatin release. Thus, leptin may be a critical hormonal signal of nutritional status in the neuroendocrine regulation of pulsatile GH secretion.

  7. 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

  8. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. [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.

  20. Effect of Deletion of Ghrelin-O-Acyltransferase on the Pulsatile Release of Growth Hormone in Mice.

    PubMed

    Xie, T Y; Ngo, S T; Veldhuis, J D; Jeffery, P L; Chopin, L K; Tschöp, M; Waters, M J; Tolle, V; Epelbaum, J; Chen, C; Steyn, F J

    2015-12-01

    Ghrelin, a gut hormone originating from the post-translational cleavage of preproghrelin, is the endogenous ligand of growth hormone secretagogue receptor 1a (GHS-R1a). Within the growth hormone (GH) axis, the biological activity of ghrelin requires octanoylation by ghrelin-O-acyltransferase (GOAT), conferring selective binding to the GHS-R1a receptor via acylated ghrelin. Complete loss of preproghrelin-derived signalling (through deletion of the Ghrl gene) contributes to a decline in peak GH release; however, the selective contribution of endogenous acyl-ghrelin to pulsatile GH release remains to be established. We assessed the pulsatile release of GH in ad lib. fed male germline goat(-/-) mice, extending measures to include mRNA for key hypothalamic regulators of GH release, and peripheral factors that are modulated relative to GH release. The amount of GH released was reduced in young goat(-/-) mice compared to age-matched wild-type mice, whereas pulse frequency and irregularity increased. Altered GH release did not coincide with alterations in hypothalamic Ghrh, Srif, Npy or Ghsr mRNA expression, or pituitary GH content, suggesting that loss of Goat does not compromise canonical mechanisms that contribute to pituitary GH production and release. Although loss of Goat resulted in an irregular pattern of GH release (characterised by an increase in the number of GH pulses observed during extended secretory events), this did not contribute to a change in the expression of sexually dimorphic GH-dependent liver genes. Of interest, circulating levels of insulin-like growth factor (IGF)-1 were elevated in goat(-/-) mice. This rise in circulating levels of IGF-1 was correlated with an increase in GH pulse frequency, suggesting that sustained or increased IGF-1 release in goat(-/-) mice may occur in response to altered GH release patterning. Our observations demonstrate that germline loss of Goat alters GH release and patterning. Although the biological relevance of

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. Brief wake episodes modulate sleep-inhibited luteinizing hormone secretion in the early follicular phase.

    PubMed

    Hall, Janet E; Sullivan, Jason P; Richardson, Gary S

    2005-04-01

    To determine the influence of sleep, sleep stage, and time of day on the dynamics of pulsatile LH secretion in the early follicular phase (EFP) of the menstrual cycle, 11 normal women underwent simultaneous polysomnographic monitoring of sleep and measurement of LH in frequent sampling studies during a 40-h protocol that consisted of one night of normal sleep and one night of sleep deprivation followed by an afternoon nap. The interpulse interval of LH was longer during sleep than wake whether it occurred at night or during the day (P < 0.002), implying a decrease in GnRH pulse frequency associated with sleep in the EFP. LH pulse amplitude was greater during sleep than wake (P < 0.001) and greater pulse amplitudes were associated with longer interpulse intervals during sleep (P < 0.005), but not wake. An interaction between sleep and time of day was observed for mean LH, with lower mean LH levels during sleep than wake at night (P < 0.02), but not during the day. Wakefulness was more likely to be associated with an LH pulse than were stages I/II, III/IV (slow wave), or rapid eye movement sleep (P < 0.005). In addition, the probability of wakefulness within the sleep episode increased 5-15 min before the onset of LH pulses (relative to randomly selected nonpulse LH; P < 0.05), suggesting that wakefulness was the primary event. In the absence of sleep, there was an effect of time of day on mean LH (P < 0.02) and LH pulse amplitude (P < 0.03), with greatest values seen during the evening. In conclusion, in the EFP, inhibition of LH pulse frequency is related to sleep rather than time of day. During periods of sleep, LH pulses occur most commonly in association with brief awakenings, suggesting that interruptions from sleep allow escape from the inhibitory effect of sleep on pulsatile GnRH secretion. A separate effect of time of day on LH pulse dynamics in the absence of sleep was also observed with evening augmentation of LH pulse amplitude and mean level; however

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. Pulsatile growth hormone and prolactin: effects of (+) butaclamol, a dopamine receptor blocking agent.

    PubMed

    Willoughby, J O; Brazeau, P; Martin, J B

    1977-10-01

    Growth hormone (rGH) and prolactin (rPRL) secretory profiles were obtained before and after treatment with a dopamine receptor blocking agent, (+) butaclamol, in 10 male rats chronically implanted with right atrial cannulae. Mean rGH plasma concentrations, determined by planimetry, were reduced (202 +/- 20 ng/ml vs. 135 +/- 20ng/ml, P less than .01), but the basic configuration and periodicity of rGH secretory bursts were unaltered. Mean rPRL plasma concentrations were elevated (11.1 +/- 2.1 ng/ml vs 65.5 +/- 8.1 ng/ml, P less than .0005), but rPRL episodic secretion was still apparent. It is concluded that dopaminergic neurons have a minor role in facilitating episodic rGH secretion. Furthermore, persisting episodic rPRL secretion in rats administered a dopamine antagonist suggests that rPRL feedback inhibition does not inactivitate the neural mechanism generating episodic rPRL secretion.

  15. '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

  16. Actions of NPY, and its Y1 and Y2 receptors on pulsatile growth hormone secretion during the fed and fasted state.

    PubMed

    Huang, Lili; Tan, Hwee Y; Fogarty, Matthew J; Andrews, Zane B; Veldhuis, Johannes D; Herzog, Herbert; Steyn, Frederik J; Chen, Chen

    2014-12-03

    The hypothalamic NPY system plays an important role in regulating food intake and energy expenditure. Different biological actions of NPY are assigned to NPY receptor subtypes. Recent studies demonstrated a close relationship between food intake and growth hormone (GH) secretion; however, the mechanism through which endogenous NPY modulates GH release remains unknown. Moreover, conclusive evidence demonstrating a role for NPY and Y-receptors in regulating the endogenous pulsatile release of GH does not exist. We used genetically modified mice (germline Npy, Y1, and Y2 receptor knock-out mice) to assess pulsatile GH secretion under both fed and fasting conditions. Deletion of NPY did not impact fed GH release; however, it reversed the fasting-induced suppression of pulsatile GH secretion. The recovery of GH secretion was associated with a reduction in hypothalamic somatotropin release inhibiting factor (Srif; somatostatin) mRNA expression. Moreover, observations revealed a differential role for Y1 and Y2 receptors, wherein the postsynaptic Y1 receptor suppresses GH secretion in fasting. In contrast, the presynaptic Y2 receptor maintains normal GH output under long-term ad libitum-fed conditions. These data demonstrate an integrated neural circuit that modulates GH release relative to food intake, and provide essential information to address the differential roles of Y1 and Y2 receptors in regulating the release of GH under fed and fasting states.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  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. 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.

  4. 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)

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. LH (Luteinizing Hormone) Test

    MedlinePlus

    ... LH and FSH may be ordered when a boy or girl does not appear to be entering puberty at ... pubic hair Growth of testicles and penis in boys Beginning of menstruation in girls ^ Back to top What does the test result ...

  14. 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.

  15. 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.

  16. 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

  17. Insulin Receptor Signaling in the GnRH Neuron Plays a Role in the Abnormal GnRH Pulsatility of Obese Female Mice

    PubMed Central

    DiVall, Sara A.; Herrera, Danny; Sklar, Bonnie; Wu, Sheng; Wondisford, Fredric; Radovick, Sally; Wolfe, Andrew

    2015-01-01

    Infertility associated with obesity is characterized by abnormal hormone release from reproductive tissues in the hypothalamus, pituitary, and ovary. These tissues maintain insulin sensitivity upon peripheral insulin resistance. Insulin receptor signaling may play a role in the dysregulation of gonadotropin-releasing hormone (GnRH) secretion in obesity, but the interdependence of hormone secretion in the reproductive axis and the multi-hormone and tissue dysfunction in obesity hinders investigations of putative contributing factors to the disrupted GnRH secretion. To determine the role of GnRH insulin receptor signaling in the dysregulation of GnRH secretion in obesity, we created murine models of diet-induced obesity (DIO) with and without intact insulin signaling in the GnRH neuron. Obese control female mice were infertile with higher luteinizing hormone levels and higher GnRH pulse amplitude and total pulsatile secretion compared to lean control mice. In contrast, DIO mice with a GnRH specific knockout of insulin receptor had improved fertility, luteinizing hormone levels approaching lean mice, and GnRH pulse amplitude and total secretion similar to lean mice. Pituitary responsiveness was similar between genotypes. These results suggest that in the obese state, insulin receptor signaling in GnRH neurons increases GnRH pulsatile secretion and consequent LH secretion, contributing to reproductive dysfunction. PMID:25780937

  18. Central lipoprivation-induced suppression of luteinizing hormone pulses is mediated by paraventricular catecholaminergic inputs in female rats.

    PubMed

    Sajapitak, Somchai; Iwata, Kinuyo; Shahab, Mohammad; Uenoyama, Yoshihisa; Yamada, Shunji; Kinoshita, Mika; Bari, Farida Y; I'Anson, Helen; Tsukamura, Hiroko; Maeda, Kei-ichiro

    2008-06-01

    The present study aims to clarify the role of fatty acids in regulating pulsatile LH secretion in rats. To produce an acute central lipoprivic condition, mercaptoacetate (MA), an inhibitor of fatty acids oxidation, was administered into the fourth cerebroventricle (4V) in ad libitum fed ovariectomized (OVX) rats (0.4, 2, and 10 micromol/rat) with or without an estradiol (E2) implant producing diestrus plasma E2 levels. Pulsatile LH secretion was suppressed by 4V MA administration in a dose-dependent manner in both OVX and OVX plus E2 rats. Mean LH levels and LH pulse frequency and amplitude were significantly reduced by the highest dose of MA in OVX rats, and by the middle and highest dose of MA in E2-treated rats, suggesting that estrogen enhanced LH suppression. Blood glucose levels increased immediately after the highest dose of MA in both groups. Fourth ventricular injection of trimetazidine (2 and 3 micromol/rat), another inhibitor of fatty acids oxidation, also inhibited pulsatile LH release, resulting in significant and dose-dependent suppression of LH pulse frequency and an increase in blood glucose levels in OVX plus E2 rats. In contrast, peripheral injection of the highest 4V dose of MA (10 micromol/rat) did not alter LH release or blood glucose levels. Microdialysis of the hypothalamic paraventricular nucleus (PVN) revealed that norepinephrine release in the region was increased by 4V MA administration. Preinjection of alpha-methyl-p-tyrosine, a catecholamine synthesis inhibitor, into the PVN completely blocked the lipoprivic inhibition of LH and the counter-regulatory increase in blood glucose levels in OVX plus E2 rats. Together, these studies indicate that fatty acid availability may be sensed by a central detector, located in the lower brainstem to maintain reproduction, and that noradrenergic inputs to the PVN mediate this lipoprivic-induced suppression of LH release.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Jointly amplified basal and pulsatile growth hormone (GH) secretion and increased process irregularity in women with anorexia nervosa: indirect evidence for disruption of feedback regulation within the GH-insulin-like growth factor I axis.

    PubMed

    Støving, R K; Veldhuis, J D; Flyvbjerg, A; Vinten, J; Hangaard, J; Koldkjaer, O G; Kristiansen, J; Hagen, C

    1999-06-01

    Anorexia nervosa (AN) is associated with multiple endocrine alterations. In the majority of AN patients, basal and GHRH-stimulated serum GH levels are increased. The metabolic effects of GH are known to be related to its pulsatile secretory pattern. The present study was performed to examine GH pulsatility in AN using the techniques of deconvolution analysis and approximate entropy, which quantify secretory activity and serial irregularity of underlying hormone release not reflected in peak occurrence or amplitudes. To this end, 24-h GH profiles were obtained by continuous blood sampling aliquoted at 20-min intervals in 8 nonfasting patients with AN [body mass index (BMI), 14.2 +/- 0.8 kg/m2; mean +/- SEM) and in 11 age-matched healthy women (BMI, 20.3 +/- 0.5 kg/m2). The deconvolution-estimated half-life of GH was not altered in the AN patients. The pituitary GH secretory burst frequency, burst mass, and burst duration were each significantly increased in women with AN compared to those in normal weight women. A 4-fold increase in daily pulsatile GH secretion was accompanied by a 20-fold increase in basal (nonpulsatile) GH secretion. There were significant negative correlations between BMI and the basal as well as pulsatile GH secretion rates. Moreover, AN patients exhibited significantly greater GH approximate entropy scores than the controls, denoting marked irregularity of the GH release process. In contrast to previous reports in healthy fasting subjects, cortisol levels in AN patients were positively correlated to GH secretion rates. Leptin levels were significantly inversely correlated to the pulsatile, but not the basal, GH secretion rate. The present data demonstrate augmented basal as well as pulsatile GH secretion with disruption of the orderliness of the GH release process in AN. Accordingly, GH secretion in AN probably reflects altered neuroendocrine feedback regulation, e.g. associated with increased hypothalamic GHRH discharge superimposed on reduced

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. A low dose euglycemic infusion of recombinant human insulin-like growth factor I rapidly suppresses fasting-enhanced pulsatile growth hormone secretion in humans.

    PubMed Central

    Hartman, M L; Clayton, P E; Johnson, M L; Celniker, A; Perlman, A J; Alberti, K G; Thorner, M O

    1993-01-01

    To determine if insulin-like growth factor I (IGF-I) inhibits pulsatile growth hormone (GH) secretion in man, recombinant human IGF-I (rhIGF-I) was infused for 6 h at 10 micrograms.kg-1.h-1 during a euglycemic clamp in 10 normal men who were fasted for 32 h to enhance GH secretion. Saline alone was infused during an otherwise identical second admission as a control. As a result of rhIGF-I infusion, total and free IGF-I concentrations increased three- and fourfold, respectively. Mean GH concentrations fell from 6.3 +/- 1.6 to 0.59 +/- 0.07 micrograms/liter after 120 min. GH secretion rates, calculated by a deconvolution algorithm, decreased with a t 1/2 of 16.6 min and remained suppressed thereafter. Suppression of GH secretion rates occurred within 60 min when total and free IGF-I concentrations were 1.6-fold and 2-fold above baseline levels, respectively, and while glucose infusion rates were < 1 mumol.kg-1.min-1. During saline infusion, GH secretion rates remained elevated. Infusion of rhIGF-I decreased the mass of GH secreted per pulse by 84% (P < 0.01) and the number of detectable GH secretory pulses by 32% (P < 0.05). Plasma insulin and glucagon decreased to nearly undetectable levels after 60 min of rhIGF-I. Serum free fatty acids, beta-hydroxybutyrate, and acetoacetate were unaffected during the first 3 h of rhIGF-I but decreased thereafter to 52, 32, and 50% of levels observed during saline. We conclude that fasting-enhanced GH secretion is rapidly suppressed by a low-dose euglycemic infusion of rhIGF-I. This effect of rhIGF-I is likely mediated through IGF-I receptors independently of its insulin-like metabolic actions. PMID:8514857

  18. 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.

  19. 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

  20. 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

  1. Relative effectiveness of carp pituitary extract, luteinizing hormone releasing hormone analog LHRHa injections and LHRHa implants for producing hybrid catfish fry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  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. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. Age-related alterations in hypothalamic kisspeptin, neurokinin B, and dynorphin neurons and in pulsatile LH release in female and male rats.

    PubMed

    Kunimura, Yuyu; Iwata, Kinuyo; Ishigami, Akihito; Ozawa, Hitoshi

    2017-02-01

    Pulsatile secretion of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) decreases during aging. Kisspeptin (encoded by Kiss1) neurons in the arcuate nucleus coexpress neurokinin B (Tac3) and dynorphin (Pdyn) and are critical for regulating the GnRH/LH pulse. We therefore examined kisspeptin neurons by histochemistry and pulsatile LH release in rats aged 2-3 (Young), 12-13 (Young-Middle), 19-22 (Late-Middle), and 24-26 (Old) months. Total LH concentrations, sampled for 3 hours, decreased in both sexes with aging. In females, numbers of Tac3 and Pdyn neurons were significantly reduced in all aging rats, and numbers of Kiss1 neurons were significantly reduced in Late-Middle and Old rats. In males, numbers of all 3 neuron-types were significantly decreased in all aging rats. GnRH agonist induced LH release in all animals; however, the increased LH concentration in all aging rats was less than that in Young rats. These results suggest that expression of each gene in kisspeptin neurons may be controlled individually during aging, and that reduction of their expression or change in pituitary responsiveness may cause attenuated pulsatile LH secretion.

  19. 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.

  20. 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

  1. Gonadotropin-releasing hormone analogs: Understanding advantages and limitations.

    PubMed

    Kumar, Pratap; Sharma, Alok

    2014-07-01

    Pituitary stimulation with pulsatile gonadotropin-releasing hormone (GnRH) analogs induces both follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Pituitary gonadotropin secretions are blocked upon desensitization when a continuous GnRH stimulus is provided by means of an agonist or when the pituitary receptors are occupied with a competitive antagonist. GnRH antagonists were not available originally; therefore, prolonged daily injections of agonist with its desensitizing effect were used. Today, single- and multiple-dose injectable antagonists are also available to block the LH surge and thus to cause desensitization. This review provides an overview of the use of GnRH analogs which is potent therapeutic agents that are considerably useful in a variety of clinical indications from the past to the future with some limitations. These indications include management of endometriosis, uterine leiomyomas, hirsutism, dysfunctional uterine bleeding, premenstrual syndrome, assisted reproduction, and some hormone-dependent tumours, other than ovulation induction.

  2. 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

  3. 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

  4. Control of gonadotropin secretion in the ovine fetus. IV. Male-specific entrainment of the hypothalamic control of luteinizing hormone secretion by testosterone in the female ovine fetus.

    PubMed

    Matwijiw, I; Faiman, C

    1991-09-01

    The role of testosterone (T) in the sex-specific entrainment of hypothalamic LH regulation was studied in five castrate and four sham-castrate chronically catheterized female fetuses androgenized by the prior administration of T cypionate (200 mg, im, every 2 weeks) to pregnant ewes from 30-86 days gestation (term = 147 days). Eight female and three male castrate fetuses served as controls. After a 2-week washout period all fetuses were operated upon in utero between 106-116 days and were studied longitudinally over a 2- to 35-day period. LH pulsatility was determined from blood samples obtained every 15 min over a standard 3-h observation period and assayed for LH by RIA (NIH LH-S16 standard). LH pulse frequency in the castrate androgenized females (41 pulses in 19 observation periods; 1 pulse/1.4 h) was significantly higher than that in non-androgenized female controls (18 pulses in 28 observation periods; 1 pulse/4.7 h observation), but was similar to that in castrate males (23 pulses in 28 observation periods; 1 pulse/1.3 h). Furthermore, LH pulse frequency in the sham castrate androgenized females (26 pulses in 13 observation periods; 1 pulse/1.5 h) was comparable to that in castrate androgenized females as well as that in castrate males. The enhanced LH pulsatility in androgenized female fetuses strongly suggests that T exposure between 30-86 days results in male-specific entrainment of hypothalamic LH regulation. Moreover, the comparable enhancement of LH pulse frequency in both sham castrate and castrate androgenized female groups suggests that in the T-exposed fetus T withdrawal alone is sufficient to result in enhanced LH pulsatility. These findings strongly suggest that T of fetal testicular origin results in male-specific entrainment of hypothalamic function and may be an important feature of male neural organization in this species.

  5. The effect of blockade of dopamine receptors on the inhibition of episodic luteinizing hormone release during electrical stimulation of the arcuate nucleus in ovariectomized rats.

    PubMed

    Gallo, R V

    1978-04-01

    This study examined the possible involvement of dopamine (DA) in mediating the inhibition of episodic LH release that occurs during electrical stimulation of the arcuate nucleus (ARH) in ovariectomized rats. Animals were treated before stimulation with pimozide (1.26--2.0 mg/kg) or d-butaclamol (1 mg/kg), blockers of DA receptors, or l-butaclamol. Apomorphine, which inhibits episodic LH release by activating DA receptors, was given near the end of the experiment to determine if these receptors were blocked. ARH stimulation suppressed pulsatile LH release in six rats when DA receptors were not blocked by pimozide (as well as two in which blockade was not tested). A transient increase occurred in one other animal. When DA receptors were blocked by pimozide, stimulation of the ARH inhibited episodic LH release in nine rats, suggesting that DA may have no role in mediating this inhibition. However, because increased LH release occurred in five additional animals, as well as in one with partial receptor blockade, the possibility remains that DA may perhaps have a minor role in this inhibitory response. Although ARH stimulation increased LH release after DA receptor blockade by d-butaclamol, this effect could not be ascribed to the DA antagonist property of this agent, because elevated blood LH levels also occurred during stimulation in rats treated with l-butaclamol, in which DA receptors were not blocked. d- and l-butaclamol may possess a non-stereospecific action on a non-dopaminergic event, thus reversing the response to ARH stimulation. Finally, whether DA receptors were blocked or not by pimozide, d-, or l-butaclamol, activation of the ventromedial hypothalamic and periventricular nucleus regions suppressed episodic LH release, but did not increase LH secretion. This suggests that the region through which stimulation can inhibit, but not increase, LH release may extend in the hypothalamus to these two areas.

  6. 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

  7. 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.

  8. Daily profiles of plasma prolactin (PRL), growth hormone (GH), insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), testosterone, and melatonin, and of pituitary PRL mRNA and GH mRNA in male Long Evans rats in acute phase of adjuvant arthritis.

    PubMed

    Roman, Olha; Seres, Janette; Herichova, Iveta; Zeman, Michal; Jurcovicova, Jana

    2003-09-01

    We studied the effects of adjuvant arthritis (AA) on the endocrine circadian rhythms of plasma prolactin (PRL), growth hormone (GH), insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), testosterone, and melatonin and of pituitary PRL and GH mRNA in male Long Evans rats. Groups of control and AA rats (studied 23 days after AA induction) that were housed under a 12/12 h light/dark cycle (light on at 06:00 h) were killed at 4 h intervals starting at 14:00 h. Cosinor analysis revealed a significant 12 h rhythm in PRL and PRL mRNA (p < 0.001) in controls with peaks at 14:00 h and 02:00 h, respectively. The peak at 02:00 h was abolished in the AA group resulting in a significant 24 h rhythm in parallel with that of PRL (p < 0.05) and PRL mRNA (p < 0.0001). Growth hormone showed no rhythm, but a significant rhythm of GH mRNA was present in both groups (p < 0.0001). Insulin-like growth factor-1 showed a 24 h rhythm in control but not in AA rats. The mean values of GH, GH mRNA, and IGF-1 were significantly reduced in AA. Luteinizing hormone displayed a significant 24 h rhythm (p < 0.01) peaking in the dark period in the control but not AA group. Testosterone showed in phase temporal changes of LH levels with AA abolishing the 02:00 h peak. Melatonin exhibited a significant 24 h rhythm in control (p < 0.001) and AA (p < 0.01) rats with maximum levels during the dark phase; the mesor value was higher in the AA males. These results demonstrate that AA interferes with the rhythms of all the studied hormones except the non-24 h (arrhythmic) GH secretion pattern and the rhythm in melatonin. The persistence of a distinct melatonin rhythm in AA suggests the observed disturbances of hormonal rhythms in this condition do not occur at the level of the pineal gland.

  9. Lutein and brain function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  10. 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.

  11. 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

  12. 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.

  13. The effects of chronic subcutaneous administration of an investigational kisspeptin analog, TAK-683, on gonadotropin-releasing hormone pulse generator activity in goats.

    PubMed

    Yamamura, Takashi; Wakabayashi, Yoshihiro; Sakamoto, Kohei; Matsui, Hisanori; Kusaka, Masami; Tanaka, Tomomi; Ohkura, Satoshi; Okamura, Hiroaki

    2014-01-01

    The continuous activation of the kisspeptin receptor by its agonists causes the abrogation of kisspeptin signaling, leading to decreased pulsatile luteinizing hormone (LH) secretion. Employing this phenomenon as a tool for probing kisspeptin action, this study aimed to clarify the role of kisspeptin in gonadotropin-releasing hormone (GnRH) pulse generation in goats. We examined the effects of chronic administration of TAK-683, an investigational kisspeptin analog, on LH secretion, GnRH immunostaining, pituitary responses to exogenous GnRH, and GnRH pulse generator activity, reflected by a characteristic increase in multiple-unit activity (MUA volley). An osmotic pump containing TAK-683 was subcutaneously implanted on day 0. TAK-683 treatment dose-dependently suppressed pulsatile LH secretion on day 1. Higher doses of chronic TAK-683 profoundly suppressed pulsatile LH secretion but had little effect on GnRH immunostaining patterns and pituitary responses to GnRH on day 5. In ovariectomized goats, MUA volleys occurred at approximately every 30 min on day -1. On day 5 of chronic TAK-683 administration, pulsatile LH secretion was markedly suppressed, whereas MUA volleys were similar to those observed on day -1. Male pheromones and senktide (neurokinin B receptor agonist) induced an MUA volley but had no effect on LH secretion during chronic TAK-683 administration. The results indicate that the chronic administration of a kisspeptin analog profoundly suppresses pulsatile LH secretion without affecting GnRH content, pituitary function or GnRH pulse generator activity, and they suggest an indispensable role for kisspeptin signaling in the cascade driving GnRH/LH pulses by the GnRH pulse generator.

  14. 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.

  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. Bioavailability and biodistribution of nanodelivered lutein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  17. Transition in Pulsatile Pipe Flow

    NASA Astrophysics Data System (ADS)

    Vlachos, Pavlos; Brindise, Melissa

    2016-11-01

    Transition has been observed to occur in the aorta, and stenotic vessels, where pulsatile flow exists. However, few studies have investigated the characteristics and effects of transition in oscillating or pulsatile flow and none have utilized a physiological waveform. In this work, we explore transition in pipe flow using three pulsatile waveforms which all maintain the same mean and maximum flow rates and range to zero flow, as is physiologically typical. Velocity fields were obtained using planar particle image velocimetry for each pulsatile waveform at six mean Reynolds numbers ranging between 500 and 4000. Turbulent statistics including turbulent kinetic energy (TKE) and Reynolds stresses were computed. Quadrant analysis was used to identify characteristics of the production and dissipation of turbulence. Coherent structures were identified using the λci method. We developed a wavelet-Hilbert time-frequency analysis method to identify high frequency structures and compared these to the coherent structures. The results of this study demonstrate that the different pulsatile waveforms induce different levels of TKE and high frequency structures, suggesting that the rates of acceleration and deceleration influence the onset and development of transition.

  18. 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.

  19. 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

  20. Hormones

    MedlinePlus

    ... affect many different processes, including Growth and development Metabolism - how your body gets energy from the foods you eat Sexual function Reproduction Mood Endocrine glands, which are special groups of cells, make hormones. The major endocrine glands are the ...

  1. 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

  2. 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).

  3. Surface obstacles in pulsatile flow

    NASA Astrophysics Data System (ADS)

    Carr, Ian A.; Plesniak, Michael W.

    2016-11-01

    Flows past obstacles mounted on flat surfaces have been widely studied due to their ubiquity in nature and engineering. For nearly all of these studies, the freestream flow over the obstacle was steady, i.e. constant velocity unidirectional flow. Unsteady, pulsatile flows occur frequently in biology, geophysics, biomedical engineering, etc. Our study is aimed at extending the comprehensive knowledge base that exists for steady flows to considerably more complex pulsatile flows. Beyond the important practical applications, characterizing the vortex and wake dynamics of flows around surface obstacles embedded in pulsatile flows can provide insights into the underlying physics in all wake and junction flows. In this study, we experimentally investigated the wake of four canonical surface obstacles: hemisphere, cube, and circular cylinders with aspect ratio of 1:1 and 2:1. Phase-averaged PIV and hot-wire anemometry are used to characterize the dynamics of coherent structures in the wake and at the windward junction of the obstacles. Complex physics occur during the deceleration phase of the pulsatile inflow. We propose a framework for understanding these physics based on self-induced vortex propagation, similar to the phenomena exhibited by vortex rings. This material is based in part upon work supported by the National Science Foundation under Grant Number CBET-1236351, and GW Centeor Biomimetics and Bioinspired Engineering (COBRE).

  4. [Pulsatile rotary pumps with low hemolysis].

    PubMed

    Qian, K; Zeng, P; Ru, W; Yuan, H; Feng, Z; Li, L

    2001-09-01

    As is well known, a pulsatile flow is important in assisted-circulation but it is difficult to produce a pulsatile flow with rotary pump, because excessive hemolysis will be generated. The authors have found that the turbulent shear is the main factor for red cell damage and therefore the key point of pulsatile rotary pumps is to reduce the turbulence by producing a pulsatile flow. In the authors' pulsatile axial pump, the pulsatile flow is obtained by axial reciprocation of constant rotating impeller; the rotation and reciprocation of the impeller are driven separately by a DC motor and a pneumatic device. Though a physiological pulsatile flow could be achieved and turbulence would not increase remarkably because the impeller rotates constantly, a second driver except a DC motor is nevertheless necessary, thus the system will become complicated. In the authors' pulsatile radial pump, a pulsatile flow is achieved by changing the rotating speed of the impeller periodically. Turbulence is minimized by a special design of twisted vanes which enable the blood flow to change its direction rather than its dimension during periodic change of rotating speed. Hemolysis tests demonstrated that the index of hemolysis(IH) of the author's pulsatile radial pump is 0.020, with is slightly more than that of the author's nonpulsatile radial pump(IH = 0.015). Animal experiments indicated that the pulsatile radial pump can assist the circulation of calves for several months without harm to blood elements and organ functions of the recipients.

  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. 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.

  7. 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.

  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. Hemodialysis using a valveless pulsatile blood pump.

    PubMed

    Lee, Kyungsoo; Mun, Cho Hae; Lee, Sa Ram; Min, Byoung Goo; Yoo, Kyu Jae; Park, Yong Woo; Won, Yong Soon

    2008-01-01

    Research on pulsatile blood pumps for extracorporeal life support has been widely performed because of the proven advantageous effects of blood pulsation. However, studies on the use of pulsatile blood pumps for hemodialysis are limited, although available evidence demonstrates that pulsatile blood flow has a positive influence on dialysis outcome. Therefore, the authors designed a new pulsatile pump, which is characterized by minimal-occlusion of blood-containing tubing, no requirement for valves, and no blood flow regurgitation. In-vitro hemolysis tests were conducted using fresh bovine blood, and the normalized index of hemolysis was adopted to compare blood traumas induced by the devised pulsatile pump and a conventional roller pump. In addition, experimental hemodialyses with a canine renal failure model were performed using the devised pump. Normalized index of hemolysis levels obtained was much smaller for the devised pulse pump (45 +/- 21 mg/100 L) than for the roller pump (103 +/- 10 mg/100 L), and no technical problems were encountered during dialysis sessions. Blood and dialysate flow rates were maintained at predetermined values and molecular removal was satisfactory. Postdialysis urea and creatinine reduction ratios were 61.8% +/- 10.6% and 57.4% +/- 9.0%, respectively. Pulsatile flow has usually been generated using pulsatile devices containing valves, but the valves cause concern in terms of the clinical applications of these devices. However, the described pulsatile pump does not require valves, and yet no blood flow regurgitation was observed.

  10. Interpreting Frequency Responses to Dose-Conserved Pulsatile Input Signals in Simple Cell Signaling Motifs

    PubMed Central

    Fletcher, Patrick A.; Clément, Frédérique; Vidal, Alexandre; Tabak, Joel; Bertram, Richard

    2014-01-01

    Many hormones are released in pulsatile patterns. This pattern can be modified, for instance by changing pulse frequency, to encode relevant physiological information. Often other properties of the pulse pattern will also change with frequency. How do signaling pathways of cells targeted by these hormones respond to different input patterns? In this study, we examine how a given dose of hormone can induce different outputs from the target system, depending on how this dose is distributed in time. We use simple mathematical models of feedforward signaling motifs to understand how the properties of the target system give rise to preferences in input pulse pattern. We frame these problems in terms of frequency responses to pulsatile inputs, where the amplitude or duration of the pulses is varied along with frequency to conserve input dose. We find that the form of the nonlinearity in the steady state input-output function of the system predicts the optimal input pattern. It does so by selecting an optimal input signal amplitude. Our results predict the behavior of common signaling motifs such as receptor binding with dimerization, and protein phosphorylation. The findings have implications for experiments aimed at studying the frequency response to pulsatile inputs, as well as for understanding how pulsatile patterns drive biological responses via feedforward signaling pathways. PMID:24748217

  11. Environmental Effects on Lutein Concent and Relationship of Lutein and Other Seed Components in Soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  12. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow generator is an electrically and pneumatically operated device used to create pulsatile blood flow....

  13. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow generator is an electrically and pneumatically operated device used to create pulsatile blood flow....

  14. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow generator is an electrically and pneumatically operated device used to create pulsatile blood flow....

  15. 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.

  16. Mechanical buckling of artery under pulsatile pressure.

    PubMed

    Liu, Qin; Han, Hai-Chao

    2012-04-30

    Tortuosity that often occurs in carotid and other arteries has been shown to be associated with high blood pressure, atherosclerosis, and other diseases. However the mechanisms of tortuosity development are not clear. Our previous studies have suggested that arteries buckling could be a possible mechanism for the initiation of tortuous shape but artery buckling under pulsatile flow condition has not been fully studied. The objectives of this study were to determine the artery critical buckling pressure under pulsatile pressure both experimentally and theoretically, and to elucidate the relationship of critical pressures under pulsatile flow, steady flow, and static pressure. We first tested the buckling pressures of porcine carotid arteries under these loading conditions, and then proposed a nonlinear elastic artery model to examine the buckling pressures under pulsatile pressure conditions. Experimental results showed that under pulsatile pressure arteries buckled when the peak pressures were approximately equal to the critical buckling pressures under static pressure. This was also confirmed by model simulations at low pulse frequencies. Our results provide an effective tool to predict artery buckling pressure under pulsatile pressure.

  17. Kisspeptin Restores Pulsatile LH Secretion in Patients with Neurokinin B Signaling Deficiencies: Physiological, Pathophysiological and Therapeutic Implications

    PubMed Central

    Young, Jacques; George, Jyothis T.; Tello, Javier A.; Francou, Bruno; Bouligand, Jerome; Guiochon-Mantel, Anne; Brailly-Tabard, Sylvie; Anderson, Richard A.; Millar, Robert P.

    2013-01-01

    Pulsatile gonadotropin-releasing hormone (GnRH) is crucial to normal reproductive function and abnormalities in pulse frequency give rise to reproductive dysfunction. Kisspeptin and neurokinin B (NKB), neuropeptides secreted by the same neuronal population in the ventral hypothalamus, have emerged recently as critical central regulators of GnRH and thus gonadotropin secretion. Patients with mutations resulting in loss of signaling by either of these neuroendocrine peptides fail to advance through puberty but the mechanisms mediating this remain unresolved. We report here that continuous kisspeptin infusion restores gonadotropin pulsatility in patients with loss-of-function mutations in NKB (TAC3) or its receptor (TAC3R), indicating that kisspeptin on its own is sufficient to stimulate pulsatile GnRH secretion. Moreover, our findings suggest that NKB action is proximal to kisspeptin in the reproductive neuroendocrine cascade regulating GnRH secretion, and may act as an autocrine modulator of kisspeptin secretion. The ability of continuous kisspeptin infusion to induce pulsatile gonadotropin secretion further indicates that GnRH neurons are able to set up pulsatile secretion in the absence of pulsatile exogenous kisspeptin. PMID:22377698

  18. Study on the effect of steady, simple pulsatile and physiological pulsatile flows through a stenosed artery

    NASA Astrophysics Data System (ADS)

    Goswami, P.; Mandal, D. K.; Manna, N. K.; Chakrabarti, S.

    2014-10-01

    In the present paper, the comparison of steady, simple pulsatile flow and physiological pulsatile flow on flow reversal zone and hemodynamic wall parameters [wall shear stress (WSS) and oscillatory shear index (OSI)] for the progression of the disease, atherosclerosis has been investigated numerically. The governing equations have been solved by finite volume method. For the numerical analysis, Womersley number, Reynolds number and percentage of restriction are taken as 10, 100 and 50 % respectively. From this study it is revealed that the separated flow from the stenosis strongly depends on inlet flow situations, the maximum chance of deposition of plaque material due to streamline contour is higher at time step t* = 0.75 for simple pulsatile flow and at time step t* = 0 for physiological pulsatile flow and this chance is lower in case of steady flow. The effect of WSS on the disease is higher in physiological pulsatile flow compared to steady as well as simple pulsatile flow. The maximum possibility of initiation as well as progression for atherosclerosis in arterial wall due to high WSS takes place at t* = 0.25 for physiological pulsatile flow. OSI indicates same length of separation for two cases of transient flow, but the rate of cyclic departure of WSS is higher in case of physiological pulsatile flow.

  19. 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.

  20. Effect of low-dose testosterone treatment on androgen regulated proteins prostate specific antigen and sex hormone binding globulin in short prepubertal boys: lack of initiation of puberty.

    PubMed

    Gupta, M K; Brown, D C; Faiman, C; Kelnar, C J H; Wu, F C W

    2003-01-01

    The efficacy of testosterone undecanoate (TU) treatment in constitutional delay of growth (CHD) is well recognized. We investigated its role in initiating puberty. Sera taken prior to, just after 6 months on and after 6 months off treatment with TU (20 mg daily) were analyzed from eight boys and compared to results from eight boys receiving placebo. Prostate specific antigen (PSA) and sex hormone binding globulin (SHBG), sleep-entrained pulsatility and mean overnight luteinizing hormone (mLH), and morning testosterone (T) levels were measured. Free androgen index (FAI) was calculated. Testicular volume (TV) and growth parameters were assessed. During treatment, there was a significant increase in height velocity in boys taking TU vs placebo (mean +/- SD: 5.7 +/- 2.0 vs 3.2 +/- 0.9 cm/year, p = 0.008) but no significant differences were observed in regard to LH pulsatility, mLH, T, SHBG, FAI, PSA and TV values. PSA was detectable in four patients (two each in the TU and placebo groups) at 6 months off treatment indicating pubertal progression. Among the hormones measured, only pretreatment mLH levels were significantly higher in the PSA-positive patients compared to 12 PSA-negative patients (mean +/- SEM: 1.5 +/- 0.39 vs 0.37 +/- 0.06 IU/l, p < 0.001). In conclusion, TU treatment shows no significant effect on initiation or advancement of puberty despite its resultant growth acceleration. Among the hormonal changes studied, mLH levels were the earliest indicator of pubertal initiation.

  1. 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.

  2. 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.

  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. Electrically actuatable smart nanoporous membrane for pulsatile drug release.

    PubMed

    Jeon, Gumhye; Yang, Seung Yun; Byun, Jinseok; Kim, Jin Kon

    2011-03-09

    We report on the fabrication of electrically responsive nanoporous membrane based on polypyrrole doped with dodecylbenzenesulfonate anion (PPy/DBS) that was electropolymerized on the upper part of anodized aluminum oxide membrane. The membrane has regular pore size and very high pore density. Utilizing a large volume change of PPy/DBS depending on electrochemical state, the pore size was acutated electrically. The actuation of the pores was experimentally confirmed by in situ atomic force microscopy and in situ flux measurement. We also demonstrated successfully pulsatile (or on-demand) drug release by using fluorescently labeled protein as a model drug. Because of a fast switching time (less than 10 s) and high flux of the drugs, this membrane could be used for emergency therapy of angina pectoris and migraine, which requires acute and on-demand drug delivery, and hormone-related disease and metabolic syndrome.

  5. 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.

  6. 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.

  7. 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.

  8. Hippocampal Fast Glutamatergic Transmission Is Transiently Regulated by Corticosterone Pulsatility

    PubMed Central

    Smeets, Johanna A. S.; Kerkhofs, Amber; Mikasova, Lenka; Karst, Henk; Groc, Laurent; Joëls, Marian

    2016-01-01

    In recent years it has become clear that corticosteroid hormones (such as corticosterone) are released in ultradian pulses as a natural consequence of pituitary-adrenal interactions. All organs, including the brain, are thus exposed to pulsatile changes in corticosteroid hormone level, important to ensure full genomic responsiveness to stress-induced surges. However, corticosterone also changes neuronal excitability through rapid non-genomic pathways, particularly in the hippocampus. Potentially, background excitability of hippocampal neurons could thus be changed by pulsatile exposure to corticosteroids. It is currently unknown, though, how neuronal activity alters during a sequence of corticosterone pulses. To test this, hippocampal cells were exposed in vitro to four consecutive corticosterone pulses with a 60 min inter-pulse interval. During the pulses we examined four features of hippocampal signal transfer by the main excitatory transmitter glutamate—i.e., postsynaptic responses to spontaneous release of presynaptic vesicles, postsynaptic GluA2-AMPA receptor dynamics, basal (evoked) field responses, and synaptic plasticity, using a set of high resolution imaging and electrophysiological approaches. We show that the first pulse of corticosterone causes a transient increase in miniature EPSC frequency, AMPA receptor trafficking and synaptic plasticity, while basal evoked field responses are unaffected. This pattern is not maintained during subsequent applications: responses become more variable, attenuate or even reverse over time, albeit with different kinetics for the various experimental endpoints. This may indicate that the beneficial effect of ultradian pulses on transcriptional regulation in the hippocampus is not consistently accompanied by short-term perturbations in background excitability. In general, this could be interpreted as a means to keep hippocampal neurons responsive to incoming signals related to environmental challenges. PMID:26741493

  9. 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...

  10. 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.

  11. 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.

  12. 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

  13. Oral pulsatile delivery: rationale and chronopharmaceutical formulations.

    PubMed

    Maroni, Alessandra; Zema, Lucia; Del Curto, Maria Dorly; Loreti, Giulia; Gazzaniga, Andrea

    2010-10-15

    Oral pulsatile/delayed delivery systems are designed to elicit programmable lag phases preceding a prompt and quantitative, repeated or prolonged release of drugs. Accordingly, they draw increasing interest because of the inherent suitability for accomplishing chronotherapeutic goals, which have recently been highlighted in connection with a number of widespread chronic diseases with typical night or early-morning recurrence of symptoms (e.g. bronchial asthma, cardiovascular disease, rheumatoid arthritis, early-morning awakening). In addition, time-based colonic release can be attained when pulsatile delivery systems are properly adapted to overcome unpredictable gastric emptying and provide delay phases that would approximately match the small intestinal transit time. Oral pulsatile delivery is pursued by means of a variety of release platforms, namely reservoir, capsular and osmotic devices. The aim of the present review is to outline the rationale and main formulation strategies behind delayed-release dosage forms intended for the pharmacological treatment of chronopathologies.

  14. Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  15. 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.

  16. 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

  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. 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.

  19. Effects of the pulsatile flow settings on pulsatile waveforms and hemodynamic energy in a PediVAS centrifugal pump.

    PubMed

    Wang, Shigang; Rider, Alan R; Kunselman, Allen R; Richardson, J Scott; Dasse, Kurt A; Undar, Akif

    2009-01-01

    The objective of this study was to test different pulsatile flow settings of the PediVAS centrifugal pump to seek an optimum setting for pulsatile flow to achieve better pulsatile energy and minimal backflow. The PediVAS centrifugal pump and the conventional pediatric clinical circuit, including a pediatric membrane oxygenator, arterial filter, arterial cannula, and 1/4 in circuit tubing were used. The circuit was primed with 40% glycerin water mixture. Postcannula pressure was maintained at 40 mm Hg by a Hoffman clamp. The experiment was conducted at 800 ml/min of pump flow with a modified pulsatile flow setting at room temperature. Pump flow and pressure readings at preoxygenator and precannula sites were simultaneously recorded by a data acquisition system. The results showed that backflows appeared at flow rates of 200-800 ml/min (200 ml/min increments) with the default pulsatile flow setting and only at 200 ml/min with the modified pulsatile flow setting. With an increased rotational speed difference ratio and a decreased pulsatile width, the pulsatility increased in terms of surplus hemodynamic energy and total hemodynamic energy at preoxygenator and precannula sites. Backflows seemed at preoxygenator and precannula sites at a 70% of rotational speed difference ratio. The modified pulsatile flow setting was better than the default pulsatile flow setting in respect to pulsatile energy and backflow. The pulsatile width and the rotational speed difference ratio significantly affected pulsatility. The parameter of the rotational speed difference ratio can automatically increase pulsatility with increased rotational speeds. Further studies will be conducted to optimize the pulsatile flow setting of the centrifugal pump.

  20. 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.

  1. [A review of drive system for pulsatile blood pump].

    PubMed

    Han, Yuan-jie; Yang, Ming

    2009-01-01

    Many varieties of pulsatile blood pumps exist in the fields of artificial hearts and ventricular assist devices. Effective sorts can be achieved with the differences in power source and transmission mechanism. Horizontal comparison across different pulsatile blood pumps, together with evolution of similar species is studied to find the commonness and evolution laws for pulsatile blood pumps. After a review of typical pulsatile blood pumps from the angle of power source and transmission mechanism, much analysis is focus on a pulsatile drive structure with flexible electro-hydraulic transmission, and importance of hydraulic transmission to improve the implantation property of pulsatile blood pumps is discussed. Finally new application of electro-hydraulic pulsatile blood pumps in the future, such as the application in Direct Mechanical Ventricular Assistant Device (DMVAD) is given.

  2. Pulsatility of Hypothalamo-Pituitary Hormones: A Challenge in Quantification

    PubMed Central

    Keenan, Daniel M.

    2015-01-01

    Neuroendocrine systems control many of the most fundamental physiological processes, e.g., reproduction, growth, adaptations to stress, and metabolism. Each such system involves the hypothalamus, the pituitary, and a specific target gland or organ. In the quantification of the interactions among these components, biostatistical modeling has played an important role. In the present article, five key challenges to an understanding of the interactions of these systems are illustrated and discussed critically. PMID:26674550

  3. How to produce a pulsatile flow with low haemolysis?

    PubMed

    Qian, K X; Zeng, P; Ru, W M; Yuan, H Y; Feng, Z G; Li, I

    2000-01-01

    It is evident that a pulsatile flow is important for blood circulation because the flow pulsatility can reduce the resistance of peripheral vessels. It is difficult, however, to produce a pulsatile flow with an impeller pump, since blood damage will occur when a pulsatile flow is produced. Further investigation has revealed that the main factor for blood damage is turbulence shear, which tears the membranes of red blood cells, resulting in free release of haemoglobin into the plasma, and consequently leads to haemolysis. Therefore, the question for developing a pulsatile impeller blood pump is: how to produce a pulsatile flow with low haemolysis? The authors have successively developed a pulsatile axial pump and a pulsatile centrifugal pump. In the pulsatile axial pump, the impeller reciprocates axially and rotates simultaneously. The reciprocation is driven by a pneumatic device and the rotation by a dc motor. For a pressure of 40 mm Hg pulsatility, about 50 mm axial reciprocating amplitude of the impeller is desirable. In order to reduce the axial amplitude, the pump inlet and the impeller both have cone-shaped heads, and the gap between the impeller and the inlet pipe changes by only 2 mm, that is the impeller reciprocates up to 2 mm and a pressure pulsatility of 40 mm Hg can be produced. As the impeller rotates with a constant speed, low turbulence in the pump may be expected. In the centrifugal pulsatile pump, the impeller changes its rotating speed periodically; the turbulence is reduced by designing an impeller with twisted vanes which enable the blood flow to change its direction rather than its magnitude during the periodic change of the rotating speed. In this way, a pulsatile flow is produced and the turbulence is minimized. Compared to the axial pulsatile pump, the centrifugal pulsatile pump needs only one driver and thus has more application possibilities. The centrifugal pulsatile pump has been used in animal experiments. The pump assisted the

  4. Nanoscaffold matrices for size-controlled, pulsatile transdermal testosterone delivery: nanosize effects on the time dimension

    NASA Astrophysics Data System (ADS)

    Malik, Ritu; Tondwal, Shailesh; Venkatesh, K. S.; Misra, Amit

    2008-10-01

    Pulsatile transdermal testosterone (T) has applications in hormone supplementation and male contraception. Pulsatile T delivery was achieved by assembling crystalline and nanoparticulate T in nucleation-inhibiting polymer matrices of controlled porosity. Different interference patterns observed from various polymeric films containing T were due to the various particle sizes of T present in the polymer matrices. Scanning electron microscopy was used to determine the size and shape of T crystals. Skin-adherent films containing T nanoparticles of any size between 10-500 nm could be prepared using pharmaceutically acceptable vinylic polymers. Drug release and skin permeation profiles were studied. The dissolution-diffusion behavior of nanoparticles differed from crystalline and molecular states. Nanosize may thus be used to engineer chronopharmacologically relevant drug delivery.

  5. 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.

  6. Pulsatile flow during cardiopulmonary bypass. Evaluation of a new pulsatile pump.

    PubMed

    Waaben, J; Andersen, K; Husum, B

    1985-01-01

    Pulsatile cardiopulmonary bypass (CPB) has been suggested to be superior to nonpulsatile CPB. This report concerns a newly developed pulsatile pump for clinical use. It is designed as a positive displacement pump, with blood allowed to collect in a valved cavity from which it is ejected by the reciprocating action of a piston. Using a uniform procedure of anaesthesia and surgery, 14 pigs were subjected to CPB at 37 degrees C for 3 hours. The pulsatile pump was used in seven pigs and a conventional roller pump in the other seven. The wave-form of the pulse during pulsatile CPB was similar to that recorded in the pigs before bypass. The values for rate of pressure change with respect to time (dp/dt) obtained in the aorta were close to the pre-CPB values. No difference was found between the two groups with respect to platelet count or haemolysis. The investigated pulsatile device appeared to be reliable and easy to handle, and the pulsation it produced closely resembled the physiologic pulse-wave form.

  7. A computer controlled pulsatile pump: preliminary study.

    PubMed

    Zwarts, M S; Topaz, S R; Jones, D N; Kolff, W J

    1996-12-01

    A Stepper Motor Driven Reciprocating Pump (SDRP) can replace roller pumps and rotary pumps for cardio pulmonary bypass, hemodialysis and regional perfusion. The blood pumping ventricles are basically the same as ventricles used for air driven artificial hearts and ventricular assist devices. The electric stepper motor uses a flexible linkage belt to produce a reciprocating movement, which pushes a hard sphere into the diaphragm of the blood ventricles. The SDRP generates pulsatile flow and has a small priming volume. The preset power level of the motor driver limits the maximum potential outflow pressure, so the driver acts as a safety device. A double pump can be made by connecting two fluid pumping chambers to opposing sides of the motor base. Each pump generates pulsatile flow. Pressure and flow studies with water were undertaken. Preliminary blood studies showed low hemolysis, even when circulating a small amount of blood up to 16 hours.

  8. 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

  9. 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

  10. Brain damage in dogs immediately following pulsatile and non-pulsatile blood flows in extracorporeal circulation

    PubMed Central

    Sanderson, J. M.; Wright, G.; Sims, F. W.

    1972-01-01

    The brains of dogs subjected to total cardiac bypass were examined for early signs of ischaemic nerve cell changes. Diffuse nerve cell changes were found immediately following two- and three-hour non-pulsatile perfusions but not following pulsatile perfusions of the same durations. The nerve cell changes found in the brains were acute cell swelling and early ischaemic cell change. Acute cell swelling was found only in the cerebellar Purkinje cells. Ischaemic cell change was found in several regions of the brain but the cerebral cortex and cerebellar Purkinje cells were most frequently affected. Diffuse nerve cell changes are attributed to non-pulsatile blood flow but some complicating factors are recognized. Focal lesions found in three brains may have been due to embolism by blood cell aggregates and/or gas microbubbles. Images PMID:5039442

  11. 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.

  12. [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.

  13. Pulsatile flow past an oscillating cylinder

    PubMed Central

    Qamar, Adnan; Seda, Robinson; Bull, Joseph L.

    2011-01-01

    A fundamental study to characterize the flow around an oscillating cylinder in a pulsatile flow environment is investigated. This work is motivated by a new proposed design of the total artificial lung (TAL), which is envisioned to provide better gas exchange. The Navier–Stokes computations in a moving frame of reference were performed to compute the dynamic flow field surrounding the cylinder. Cylinder oscillations and pulsatile free-stream velocity were represented by two sinusoidal waves with amplitudes A and B and frequencies ωc and ω, respectively. The Keulegan–Carpenter number (Kc=Uo∕Dωc) was used to describe the frequency of the oscillating cylinder while the pulsatile free-stream velocity was fixed by imposing ω∕Kc=1 for all cases investigated. The parameters of interest and their values were amplitude (0.5D

  14. Pulsatile flow past an oscillating cylinder

    NASA Astrophysics Data System (ADS)

    Qamar, Adnan; Seda, Robinson; Bull, Joseph L.

    2011-04-01

    A fundamental study to characterize the flow around an oscillating cylinder in a pulsatile flow environment is investigated. This work is motivated by a new proposed design of the total artificial lung (TAL), which is envisioned to provide better gas exchange. The Navier-Stokes computations in a moving frame of reference were performed to compute the dynamic flow field surrounding the cylinder. Cylinder oscillations and pulsatile free-stream velocity were represented by two sinusoidal waves with amplitudes A and B and frequencies ωc and ω, respectively. The Keulegan-Carpenter number (Kc=Uo/Dωc) was used to describe the frequency of the oscillating cylinder while the pulsatile free-stream velocity was fixed by imposing ω /Kc=1 for all cases investigated. The parameters of interest and their values were amplitude (0.5D

  15. 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.

  16. Pulsatile Flow Studies in Atherosclerotic Carotid Bifurcations

    NASA Astrophysics Data System (ADS)

    Bale-Glickman, Jocelyn; Selby, Kathy; Saloner, David; Savas, Omer

    2001-11-01

    Particle image velocimetry and flow visualization techniques are used to study flows in models of atherosclerotic carotid bifurcations. The flow models exactly replicate the interior geometry of plaque excised from patients. The input flows are physiological wave forms derived from Doppler Ultrasound scans done on patients before surgery. The systolic and diastolic Reynolds numbers are 300 and 900. The complex internal geometry of the diseased artery combined with the pulsatile input flow results in exceedingly complex flow patterns. These flow patterns include internal jets, three-dimensional shear layers, stagnation lines, and multiple recirculation and separation regions. The physiological input flows are compared to flows when the wave form is sinusoidal.

  17. Detection and measurement of retinal blood vessel pulsatile motion

    NASA Astrophysics Data System (ADS)

    Xiao, Di; Frost, Shaun; Vignarajan, Janardhan; An, Dong; Tay-Kearney, Mei-Ling; Kanagasingam, Yogi

    2016-03-01

    Retinal photography is a non-invasive and well-accepted clinical diagnosis of ocular diseases. Qualitative and quantitative assessment of retinal images is crucial in ocular diseases related clinical application. Pulsatile properties caused by cardiac rhythm, such as spontaneous venous pulsation (SVP) and pulsatile motion of small arterioles, can be visualized by dynamic retinal imaging techniques and provide clinical significance. In this paper, we aim at vessel pulsatile motion detection and measurement. We proposed a novel approach for pulsatile motion measurement of retinal blood vessels by applying retinal image registration, blood vessel detection and blood vessel motion detection and measurement on infrared retinal image sequences. The performance of the proposed methods was evaluated on 8 image sequences with 240 images. A preliminary result has demonstrated the good performance of the method for blood vessel pulsatile motion observation and measurement.

  18. 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.

  19. 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.

  20. Pulsatile flow past a single oscillating cylinder

    NASA Astrophysics Data System (ADS)

    Seda, Robinson; Qamar, Adnan; Bull, Joseph

    2010-11-01

    The potential for oscillating fibers to modify flow within a new artificial lung design is first examined in the present fundamental fluid mechanics study of flow past a single oscillating cylinder. This new design is intended to provide better gas exchange through vorticity enhancement by oscillating microfibers (cylinders) in a pulsatile flow environment. The Keulegan-Carpenter number (Kc=Uo/Dφc) was used to describe the frequency of the oscillating cylinder (φc) while the pulsatile free stream velocity was fixed by imposing φ/Kc=1 for all cases investigated. The parameters investigated in this study were amplitude of oscillation (0.5D

  1. Pulsatile Dynamics in the Yeast Proteome

    PubMed Central

    Dalal, Chiraj K.; Cai, Long; Lin, Yihan; Rahbar, Kasra; Elowitz, Michael B.

    2014-01-01

    The activation of transcription factors in response to environmental conditions is fundamental to cellular regulation. Recent work has revealed that some transcription factors are activated in stochastic pulses of nuclear localization, rather than at a constant level, even in a constant environment. In such cases, signals control the mean activity of the transcription factor by modulating the frequency, duration, or amplitude of these pulses. Although specific pulsatile transcription factors have been identified in diverse cell types, it has remained unclear how prevalent pulsing is within the cell, how variable pulsing behaviors are between genes, and whether pulsing is specific to transcriptional regulators or employed more broadly. To address these issues, we performed a proteome-wide movie-based screen to systematically identify localization-based pulsing behaviors in Saccharomyces cerevisiae. The screen examined all genes in a previously developed fluorescent protein fusion library of 4159 strains in multiple media conditions. This approach revealed stochastic pulsing in 10 proteins, all transcription factors. In each case, pulse dynamics were heterogeneous and unsynchronized among cells in clonal populations. Pulsing is the only dynamic localization behavior we observed, and it tends to occur in pairs of paralagous and redundant proteins. Taken together, these results suggest that pulsatile dynamics play a pervasive role in yeast and may be similarly prevalent in other eukaryotic species. PMID:25220054

  2. Effects of continuous and pulsatile PTH treatments on rat bone marrow stromal cells

    SciTech Connect

    Yang Chiming; Frei, Hanspeter Burt, Helen M.; Rossi, Fabio

    2009-03-20

    Bone marrow stromal cells (MSCs) differentiation and proliferation are controlled by numerous growth factors and hormones. Continuous parathyroid hormone (PTH) treatment has been shown to decrease osteoblast differentiation, whereas pulsatile PTH increases osteoblast differentiation. However, the effects of PTH treatments on MSCs have not been investigated. This study showed continuous PTH treatment in the presence of dexamethasone (DEX) promoted osteogenic differentiation of rat MSCs in vitro, as demonstrated by increased alkaline phosphatase (ALP) activity, number of ALP expressing cells, and up-regulation of PTH receptor-1, ALP, and osteocalcin mRNA expressions. In contrast, pulsatile PTH treatment was found to suppress osteogenesis of rat MSCs, possibly by promoting the maintenance of undifferentiated cells. Additionally, the observed effects of PTH were strongly dependent on the presence of DEX. MSC proliferation however was not influenced by PTH independent of treatment regimen and presence or absence of DEX. Furthermore, our work raised the possibility that PTH treatment may modulate stem/progenitor cell activity within MSC cultures.

  3. A Novel Rotary Pulsatile Flow Pump for Cardiopulmonary Bypass

    PubMed Central

    Teman, Nicholas R.; Mazur, Daniel E.; Toomasian, John; Jahangir, Emilia; Alghanem, Fares; Goudie, Marcus; Rojas-Peña, Alvaro; Haft, Jonathan W.

    2014-01-01

    It has been suggested that pulsatile blood flow is superior to continuous flow in cardiopulmonary bypass (CPB). However, adoption of pulsatile flow (PF) technology has been limited due to practically and complexity of creating a consistent physiologic pulse. A pediatric pulsatile rotary ventricular pump (PRVP) was designed to address this problem. We evaluated the PRVP in an animal model, and determined its ability to generate PF during CPB. The PRVP (modified peristaltic pump, with tapering of the outlet of the pump chamber) was tested in 4 piglets (10-12kg). Cannulation was performed with right atrial and aortic cannulae, and pressure sensors were inserted into the femoral arteries. Pressure curves were obtained at different levels of flow and compared with both the animal's baseline physiologic function and a continuous flow (CF) roller pump. Pressure and flow waveforms demonstrated significant pulsatility in the PRVP setup compared to CF at all tested conditions. Measurement of hemodynamic energy data, including the percent pulsatile energy and the surplus hydraulic energy, also revealed a significant increase in pulsatility with the PRVP (p <0.001). PRVP creates physiologically significant PF, similar to the pulsatility of a native heart, and has the potential to be easily implemented in pediatric CPB. PMID:24625536

  4. 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.

  5. 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.

  6. Pulsatile Flow Studies in Atherosclerotic Carotid Bifurcation

    NASA Astrophysics Data System (ADS)

    Bale-Glickman, Jocelyn; Selby, Kathy; Saloner, David; Savas, Omer

    2002-11-01

    Particle image velocimetry and flow visualization techniques are used to study flow in models of atherosclerotic carotid bifurcations. The models exactly replicate the interior geometry of plaque excised from patients. The input flow is a physiological waveform derived from Doppler Ultrasound scans done on the patients before surgery. The systolic and diastolic Reynolds numbers are 200 and 900 respectively. The complex internal geometry of the diseased artery combined with the pulsatile input flows give exceedingly complex flow patterns. These flow patterns include internal jets, three-dimensional shear layers, stagnation lines, and multiple recirculation and separation regions. Ensemble averaged and instantaneous flow fields are compared. Wall shear stresses at the stenoses are estimated to be on the order of 10 PA. The physiological input flows are also compared to flows when the waveform is sinusoidal.

  7. Optimal Branching Asymmetry of Hydrodynamic Pulsatile Trees

    NASA Astrophysics Data System (ADS)

    Florens, Magali; Sapoval, Bernard; Filoche, Marcel

    2011-04-01

    Most of the studies on optimal transport are done for steady state regime conditions. Yet, there exists numerous examples in living systems where supply tree networks have to deliver products in a limited time due to the pulsatile character of the flow, as it is the case for mammalian respiration. We report here that introducing a systematic branching asymmetry allows the tree to reduce the average delivery time of the products. It simultaneously increases its robustness against the inevitable variability of sizes related to morphogenesis. We then apply this approach to the human tracheobronchial tree. We show that in this case all extremities are supplied with fresh air, provided that the asymmetry is smaller than a critical threshold which happens to match the asymmetry measured in the human lung. This could indicate that the structure is tuned at the maximum asymmetry level that allows the lung to feed all terminal units with fresh air.

  8. 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.

  9. 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

  10. Suppressive effects of long-term exposure to P-nitrophenol on gonadal development, hormonal profile with disruption of tissue integrity, and activation of caspase-3 in male Japanese quail (Coturnix japonica).

    PubMed

    Ahmed, Eman; Nagaoka, Kentaro; Fayez, Mostafa; Abdel-Daim, Mohamed M; Samir, Haney; Watanabe, Gen

    2015-07-01

    P-Nitrophenol (PNP) is considered to be one of nitrophenol derivatives of diesel exhaust particles. PNP is a major metabolite of some organophosphorus compounds. PNP is a persistent organic pollutant as well as one of endocrine-disrupting compounds. Consequently, bioaccumulation of PNP potentiates toxicity. The objectives of the current study were to assess in vivo adverse effects of long-term low doses of PNP exposure on reproductive system during development stage. Twenty-eight-day-old male Japanese quails were orally administered different doses of PNP (0, 0.01, 0.1, 1 mg/kg body weight) daily for 2.5 months. Testicular histopathology, hormones, caspase-3 (CASP3), and claudin-1 (CLDN1) tight junction protein, as well as plasma hormones were analyzed. The results revealed that long-term PNP exposure caused testicular histopathological changes such as vacuolation of spermatogenic cell and spermatocyte with significant testicular and cloacal gland atrophy. PNP activated CASP3 enzyme that is an apoptosis-related cysteine peptidase. Besides, it disrupted the expression of CLDN1. Furthermore, a substantial decrease in plasma concentrations of luteinizing hormone (LH) and testosterone was observed after 2 and 2.5 months in the PNP-treated groups. Meanwhile, the pituitary LH did not significantly change. Site of action of PNP may be peripheral on testicular development and/or centrally on the hypothalamic-pituitary-gonadal axis through reduction of pulsatile secretion of gonadotrophin-releasing hormone. Consequently, it may reduce the sensitivity of the anterior pituitary gland to secrete LH. In conclusion, PNP induced profound endocrine disruption in the form of hormonal imbalance, induction of CASP3, and disruption of CLDN1 expression in the testis. Hence, it may hinder the reproductive processes.

  11. 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.

  12. 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.

  13. 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

  14. Optimum Heart Rate to Minimize Pulsatile External Cardiac Power

    NASA Astrophysics Data System (ADS)

    Pahlevan, Niema; Gharib, Morteza

    2011-11-01

    The workload on the left ventricle is composed of steady and pulsatile components. Clinical investigations have confirmed that an abnormal pulsatile load plays an important role in the pathogenesis of left ventricular hypertrophy (LVH) and progression of LVH to congestive heart failure (CHF). The pulsatile load is the result of the complex dynamics of wave propagation and reflection in the compliant arterial vasculature. We hypothesize that aortic waves can be optimized to reduce the left ventricular (LV) pulsatile load. We used an in-vitro experimental approach to investigate our hypothesis. A unique hydraulic model was used for in-vitro experiments. This model has physical and dynamical properties similar to the heart-aorta system. Different compliant models of the artificial aorta were used to test the hypothesis under various aortic rigidities. Our results indicate that: i) there is an optimum heart rate that minimizes LV pulsatile power (this is in agreement with our previous computational study); ii) introducing an extra reflection site at the specific location along the aorta creates constructive wave conditions that reduce the LV pulsatile power.

  15. Measuring blood oxygenation of pulsatile arteries using photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Li, Qian; Yu, Tianhao; Li, Lin; Chai, Xinyu; Zhou, Chuanqing

    2016-10-01

    Heart pumps blood through the blood vessels to provide body with oxygen and nutrients. As the result, the blood flow, volume and oxygenation in arteries has a pulsatile nature. Measuring these pulsatile parameters enables more precise monitoring of oxygen metabolic rate and is thus valuable for researches and clinical applications. Photoacoustic microscopy (PAM) is a proven label-free method for in vivo measuring blood oxygenation at single blood vessel level. However, studies using PAM to observe the pulsatile nature of blood oxygenation in arteries were not reported. In this paper, we use optical-resolution PAM (OR-PAM) technology to study the blood oxygenation dynamics of pulsatile arteries. First, the ability of our OR-PAM system to accurately reflect the change of optical absorption in imaged objects is demonstrated in a phantom study. Then the system is used to image exposed cortical blood vessels of cat. The pulsatile nature of blood volume and oxygenation in arteries is clearly reflected in photoacoustic (PA) signals, whereas it's not observable in veins. By using a multi-wavelength laser, the dynamics of the blood oxygenation of pulsatile arteries in cardiac cycles can be measured, based on the spectroscopic method.

  16. The impact of pump settings on the quality of pulsatility.

    PubMed

    Rider, Alan R; Ressler, Noel M; Karkhanis, Tushar R; Kunselman, Allen R; Wang, Shigang; Undar, Akif

    2009-01-01

    The study objective was to evaluate the Jostra HL-20 roller pump under different baseflow and pump head settings with quantified energy values from pressure and flow waveforms, in a simulated pediatric bypass circuit. Pump flow rate was set at 800 mL/min for both pulsatile and nonpulsatile perfusion modes and the mean arterial pressure (MAP) of the pseudopatient was maintained at 40 mm Hg for each experiment. Pulsatile baseflow settings and pump head start points varied with each experiment. Pressure and flow waveforms were recorded at preoxygenator, precannula, and postcannula sites under each pump setting. A total of 91 experiments were performed (n=7, nonpulsatile; n=84, pulsatile). Increasing baseflow caused decreases in the mean circuit pressure and surplus hemodynamic energy (SHE) levels for all pump head start times. When increasing pump head start time within each baseflow, values for MAP and SHE increased significantly. Regardless of baseflow or pump head start time, values for mean circuit pressure and SHE were lower for nonpulsatile flow than for pulsatile flow. Total hemodynamic energy values were also significantly higher under pulsatile perfusion and increased pump start times while decreasing with increased baseflows in the circuit. This study concludes that decreased baseflows with increased pump head settings on the Jostra HL-20 roller pump could significantly increase quality of generated pulsatile energy. Further research is necessary to evaluate these various pump settings under microembolic loads and with different circuit components.

  17. Effect of echo artifacts on characterization of pulsatile tissues in neonatal cranial ultrasonic movies

    NASA Astrophysics Data System (ADS)

    Fukuzawa, Masayuki; Takahashi, Kazuki; Tabata, Yuki; Kitsunezuka, Yoshiki

    2016-04-01

    Effect of echo artifacts on characterization of pulsatile tissues has been examined in neonatal cranial ultrasonic movies by characterizing pulsatile intensities with different regions of interest (ROIs). The pulsatile tissue, which is a key point in pediatric diagnosis of brain tissue, was detected from a heartbeat-frequency component in Fourier transform of a time-variation of 64 samples of echo intensity at each pixel in a movie fragment. The averages of pulsatile intensity and power were evaluated in two ROIs: common fan-shape and individual cranial-shape. The area of pulsatile region was also evaluated as the number of pixels where the pulsatile intensity exceeds a proper threshold. The extracranial pulsatile region was found mainly in the sections where mirror image was dominant echo artifact. There was significant difference of pulsatile area between two ROIs especially in the specific sections where mirror image was included, suggesting the suitability of cranial-shape ROI for statistical study on pulsatile tissues in brain. The normalized average of pulsatile power in the cranial-shape ROI exhibited most similar tendency to the normalized pulsatile area which was treated as a conventional measure in spite of its requirement of thresholding. It suggests the potential of pulsatile power as an alternative measure for pulsatile area in further statistical study of pulsatile tissues because it was neither affected by echo artifacts nor threshold.

  18. A new method of providing pulsatile flow in a centrifugal pump: assessment of pulsatility using a mock circulatory system.

    PubMed

    Herreros, Jesús; Berjano, Enrique J; Sales-Nebot, Laura; Más, Pedro; Calvo, Irene; Mastrobuoni, Stefano; Mercé, Salvador

    2008-06-01

    Previous studies have demonstrated the potential advantages of pulsatile flow as compared with continuous flow. However, to date, physiologic pumps have been technically complex and their application has therefore remained in the experimental field. We have developed a new type of centrifugal pump, which can provide pulsatile as well as continuous flow. The inner wall of a centrifugal pump is pulsed by means of a flexible membrane, which can be accurately controlled by means of either a hydraulic or pneumatic driver. The aim of this study was to assess the hydraulic behavior of the new pump in terms of surplus hemodynamic energy (SHE). We conducted experiments using a mock circulatory system including a membrane oxygenator. No differences were found in the pressure-flow characteristics between the new pump and a conventional centrifugal pump, suggesting that the inclusion of the flexible membrane does not alter hydraulic performance. The value of SHE rose when systolic volume was increased. However, SHE dropped when the percentage of ejection time was reduced and also when the continuous flow (programmed by the centrifugal console) increased. Mean flow matched well with the continuous flow set by the centrifugal console, that is, the pulsatile component of the flow was exclusively controlled by the pulsatile console, and was therefore independent of the continuous flow programmed by the centrifugal console. The pulsatility of the new pump was approximately 25% of that created with a truly pulsatile pump.

  19. 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

  20. Pulsatile blood flow in Abdominal Aortic Aneurysms

    NASA Astrophysics Data System (ADS)

    Salsac, Anne-Virginie; Lasheras, Juan C.; Singel, Soeren; Varga, Chris

    2001-11-01

    We discuss the results of combined in-vitro laboratory measurements and clinical observations aimed at determining the effect that the unsteady wall shear stresses and the pressure may have on the growth and eventual rupturing of an Abdominal Aortic Aneurysm (AAA), a permanent bulging-like dilatation occurring near the aortic bifurcation. In recent years, new non-invasive techniques, such as stenting, have been used to treat these AAAs. However, the development of these implants, aimed at stopping the growth of the aneurysm, has been hampered by the lack of understanding of the effect that the hemodynamic forces have on the growth mechanism. Since current in-vivo measuring techniques lack the precision and the necessary resolution, we have performed measurements of the pressure and shear stresses in laboratory models. The models of the AAA were obtained from high resolution three-dimensional CAT/SCANS performed in patients at early stages of the disease. Preliminary DPIV measurements show that the pulsatile blood flow discharging into the cavity of the aneurysm leads to large spikes of pressure and wall shear stresses near and around its distal end, indicating a possible correlation between the regions of high wall shear stresses and the observed location of the growth of the aneurysm.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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: ...

  8. Stabilizing control for a pulsatile cardiovascular mathematical model.

    PubMed

    de los Reyes, Aurelio A; Jung, Eunok; Kappel, Franz

    2014-06-01

    In this paper, we develop a pulsatile model for the cardiovascular system which describes the reaction of this system to a submaximal constant workload imposed on a person at a bicycle ergometer test after a period of rest. Furthermore, the model should allow to use measurements for the pulsatile pressure in fingertips which provide information on the diastolic and the systolic pressure for parameter estimation. Based on the assumption that the baroreceptor loop is the essential control loop in this case, we design a stabilizing feedback control for the pulsatile model which is obtained by solving a linear-quadratic regulator problem for the linearization of a non-pulsatile counterpart of the pulsatile model. We also investigate the behavior of the model with respect to changes in the weight of the term in the cost functional for the linear-quadratic regulator problem which penalizes the deviation of the momentary pressure in the aorta from the pressure at the stationary situation which should be obtained.

  9. Human endothelial cell responses to cardiovascular inspired pulsatile shear stress

    NASA Astrophysics Data System (ADS)

    Watson, Matthew; Baugh, Lauren; Black, Lauren, III; Kemmerling, Erica

    2016-11-01

    It is well established that hemodynamic shear stress regulates blood vessel structure and the development of vascular pathology. This process can be studied via in vitro models of endothelial cell responses to pulsatile shear stress. In this study, a macro-scale cone and plate viscometer was designed to mimic various shear stress waveforms found in the body and apply these stresses to human endothelial cells. The device was actuated by a PID-controlled DC gear-motor. Cells were exposed to 24 hours of pulsatile shear and then imaged and stained to track their morphology and secretions. These measurements were compared with control groups of cells exposed to constant shear and no shear. The results showed that flow pulsatility influenced levels of secreted proteins such as VE-cadherin and neuroregulin IHC. Cell morphology was also influenced by flow pulsatility; in general cells exposed to pulsatile shear stress developed a higher aspect ratio than cells exposed to no flow but a lower aspect ratio than cells exposed to steady flow.

  10. Effects of non-pulsatile flow on thrombogenesis

    NASA Astrophysics Data System (ADS)

    Metcalfe, Ralph; Harting, Matthew; Delgado, Reynolds; Frazier, O. Howard

    2002-11-01

    Congestive heart failure afflicts 4.5 million people in the US alone, with an average 5-year mortality of more than 50%. Among the most promising treatments for this condition are VADs (ventricular assist devices). While conventional pulsatile flow VADs are large and introduce some significant complications such as thrombosis, non-pulsatile axial flow VADs have potentially significant advantages in being smaller, with smaller thrombogenic surfaces. However, the long term effects of non-pulsatile flow on the vascular system are not well understood. We have investigated the effects of pulsatility of blood flow in the stenotic human carotid artery using unsteady, three-dimensional computational fluid dynamic simulations. We have found that permanent, low shear stagnation zones can develop distal to stenoses with non-pulsatile flow, potentially leading to thrombus formation. In contrast, systolic peak flow tends to flush out such stagnation zones. These results are consistent with observed thrombus formation in two patients who underwent implantation of a Jarvik 2000 LVAD.

  11. Functional tissue pulsatility imaging of the brain during visual stimulation.

    PubMed

    Kucewicz, John C; Dunmire, Barbrina; Leotta, Daniel F; Panagiotides, Heracles; Paun, Marla; Beach, Kirk W

    2007-05-01

    Functional tissue pulsatility imaging is a new ultrasonic technique being developed to map brain function by measuring changes in tissue pulsatility as a result of changes in blood flow with neuronal activation. The technique is based in principle on plethysmography, an older, nonultrasound technology for measuring expansion of a whole limb or body part as a result of perfusion. Perfused tissue expands by a fraction of a percent early in each cardiac cycle when arterial inflow exceeds venous outflow, and it relaxes later in the cardiac cycle when venous drainage dominates. Tissue pulsatility imaging (TPI) uses tissue Doppler signal processing methods to measure this pulsatile "plethysmographic" signal from hundreds or thousands of sample volumes in an ultrasound image plane. A feasibility study was conducted to determine if TPI could be used to detect regional brain activation during a visual contrast-reversing checkerboard block paradigm study. During a study, ultrasound data were collected transcranially from the occipital lobe as a subject viewed alternating blocks of a reversing checkerboard (stimulus condition) and a static, gray screen (control condition). Multivariate analysis of variance was used to identify sample volumes with significantly different pulsatility waveforms during the control and stimulus blocks. In 7 of 14 studies, consistent regions of activation were detected from tissue around the major vessels perfusing the visual cortex.

  12. Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes

    PubMed Central

    Satin, Leslie S.; Butler, Peter C.; Ha, Joon; Sherman, Arthur S.

    2015-01-01

    Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM. PMID:25637831

  13. A turbulence model for pulsatile arterial flows.

    PubMed

    Younis, B A; Berger, S A

    2004-10-01

    Difficulties in predicting the behavior of some high Reynolds number flows in the circulatory system stem in part from the severe requirements placed on the turbulence model chosen to close the time-averaged equations of fluid motion. In particular, the successful turbulence model is required to (a) correctly capture the "nonequilibrium" effects wrought by the interactions of the organized mean-flow unsteadiness with the random turbulence, (b) correctly reproduce the effects of the laminar-turbulent transitional behavior that occurs at various phases of the cardiac cycle, and (c) yield good predictions of the near-wall flow behavior in conditions where the universal logarithmic law of the wall is known to be not valid. These requirements are not immediately met by standard models of turbulence that have been developed largely with reference to data from steady, fully turbulent flows in approximate local equilibrium. The purpose of this paper is to report on the development of a turbulence model suited for use in arterial flows. The model is of the two-equation eddy-viscosity variety with dependent variables that are zero-valued at a solid wall and vary linearly with distance from it. The effects of transition are introduced by coupling this model to the local value of the intermittency and obtaining the latter from the solution of a modeled transport equation. Comparisons with measurements obtained in oscillatory transitional flows in circular tubes show that the model produces substantial improvements over existing closures. Further pulsatile-flow predictions, driven by a mean-flow wave form obtained in a diseased human carotid artery, indicate that the intermittency-modified model yields much reduced levels of wall shear stress compared to the original, unmodified model. This result, which is attributed to the rapid growth in the thickness of the viscous sublayer arising from the severe acceleration of systole, argues in favor of the use of the model for the

  14. Lutein nanocrystals as antioxidant formulation for oral and dermal delivery.

    PubMed

    Mitri, Khalil; Shegokar, Ranjita; Gohla, Sven; Anselmi, Cecilia; Müller, Rainer H

    2011-11-25

    Lutein is a well known antioxidant and anti-free radical used in cosmetic, nutraceutical industry with potential application in pharmaceutics as supportive antioxidant in treatments. As lipophilic molecule it is poorly soluble in water and has a low bioavailability. Lutein nanosuspension was prepared to enhance dissolution velocity, saturation solubility (C(s)), which are major factors determining oral bioavailability and penetration into the skin. High pressure homogenization (HPH) was used to prepare lutein nanosuspension. Particle size was determined by photon correlation spectroscopy (PCS) and laser diffractometry (LD). The lowest PCS diameter obtained was about 429 nm, the LD diameter 90% of 1.2 μm. The zeta potential was about -40 mV in water and -17 mV in the original dispersion medium. The 3 month storage study at different temperatures (4°C, 25°C, 40°C) confirmed physical stability despite the low zeta potential of -17 mV in original surfactant solution. A pronounced increase in saturation solubility by 26.3 fold was obtained for lutein nanocrystals compared to coarse powder. The lutein nanosuspension was converted into pellets and filled into hard gelatin capsules for nutraceutical use, showed a superior in vitro release (factor of 3-4). Lyophilized nanosuspension was prepared for subsequent incorporation into creams and gels. The lyophilized nanosuspension was very well re-dispersible (435 nm). Using cellulose nitrate membranes as in vitro model, permeation through this barrier was 14× higher for lutein nanocrystals compared to coarse powder. However, pig ear skin did not allow lutein to permeate but supported localization of the lutein in the skin where it should act anti-oxidatively.

  15. 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.

  16. 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

  17. [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.

  18. Numerical simulation of pulsatile flow in rough pipes

    NASA Astrophysics Data System (ADS)

    Chin, Cheng; Monty, Jason; Ooi, Andrew; Illingworth, Simon; Marusic, Ivan; Skvortsov, Alex

    2016-11-01

    Direct numerical simulation (DNS) of pulsatile turbulent pipe flow is carried out over three-dimensional sinusoidal surfaces mimicking surface roughness. The simulations are performed at a mean Reynolds number of Reτ 540 (based on friction velocity, uτ, and pipe radii, δ) and at various roughness profiles following the study of Chan et al., where the size of the roughness (roughness semi-amplitude height h+ and wavelength λ+) is increased geometrically while maintaining the height-to-wavelength ratio of the sinusoidal roughness element. Results from the pulsatile simulations are compared with non-pulsatile simulations to investigate the effects of pulsation on the Hama roughness function, ΔU+ . Other turbulence statistics including mean turbulence intensities, Reynolds stresses and energy spectra are analysed. In addition, instantaneous phase (eg. at maximum and minimum flow velocities) and phase-averaged flow structures are presented and discussed.

  19. Entrainment and thrust augmentation in pulsatile ejector flows

    NASA Technical Reports Server (NTRS)

    Sarohia, V.; Bernal, L.; Bui, T.

    1981-01-01

    This study comprised direct thrust measurements, flow visualization by use of a spark shadowgraph technique, and mean and fluctuating velocity measurements with a pitot tube and linearized constant temperature hot-wire anemometry respectively. A gain in thrust of as much as 10 to 15% was observed for the pulsatile ejector flow as compared to the steady flow configuration. From the velocity profile measurements, it is concluded that this enhanced augmentation for pulsatile flow as compared to a nonpulsatile one was accomplished by a corresponding increased entrainment by the primary jet flow. It is also concluded that the augmentation and total entrainment by a constant area ejector critically depends upon the inlet geometry of the ejector. Experiments were performed to evaluate the influence of primary jet to ejector area ratio, ejector length, and presence of a diffuser on pulsatile ejector performance.

  20. 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.

  1. Flush-mounted hot film anemometer accuracy in pulsatile flow.

    PubMed

    Nandy, S; Tarbell, J M

    1986-08-01

    The accuracy of a flush-mounted hot film anemometer probe for wall shear stress measurements in physiological pulsatile flows was evaluated in fully developed pulsatile flow in a rigid straight tube. Measured wall shear stress waveform based on steady flow anemometer probe calibrations were compared to theoretical wall shear stress waveforms based on well-established theory and measured flow rate waveforms. The measured and theoretical waveforms were in close agreement during systole (average deviation of 14 percent at peak systole). As expected, agreement was poor during diastole because of flow reversal and diminished frequency response at low shear rate.

  2. 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...

  3. 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.

  4. Hormonal Control of Breast Cancer Cell Growth.

    DTIC Science & Technology

    1998-09-01

    known function , which is virtually identical to that of the pituitary luteinizing hormone (LH), is the stimulation of the production of gonadal...HI-1 did not match any previously identified genes, appearing to be a novel gene whose function might be related with process of differentiation. Its...in and in vitro (112-121) indicates that further identification of the functional role of this protein and of others whose synthesis is stimulated by

  5. Novel Strip Test for Circulating Hormones

    DTIC Science & Technology

    1996-10-01

    level of discrimination will permit 72 hour advance notice of impending ovulation , making the strips a useful tool in family planning in that they...provide sufficient advance notice of ovulation to allow for the lifetime of sperm in the vagina. To implement this novel immunoassay technology, a new...before the peak of luteinizing hormone (LH) until two days after the peak.’ The maximum notification of impending ovulation provided by measurement

  6. Noninvasive pulsatile flow estimation for an implantable rotary blood pump.

    PubMed

    Karantonis, Dean M; Cloherty, Shaun L; Mason, David G; Ayre, Peter J; Lovell, Nigel H

    2007-01-01

    A noninvasive approach to the task of pulsatile flow estimation in an implantable rotary blood pump (iRBP) has been proposed. Employing six fluid solutions representing a range of viscosities equivalent to 20-50% blood hematocrit (HCT), pulsatile flow data was acquired from an in vitro mock circulatory loop. The entire operating range of the pump was examined, including flows from -2 to 12 L/min. Taking the pump feedback signals of speed and power, together with the HCT level, as input parameters, several flow estimate models were developed via system identification methods. Three autoregressive with exogenous input (ARX) model structures were evaluated: structures I and II used the input parameters directly; structure II incorporated additional terms for HCT; and the third structure employed as input a non-pulsatile flow estimate equation. Optimal model orders were determined, and the associated models yielded minimum mean flow errors of 5.49% and 0.258 L/min for structure II, and 5.77% and 0.270 L/min for structure III, when validated on unseen data. The models developed in this study present a practical method of accurately estimating iRBP flow in a pulsatile environment.

  7. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass pulsatile flow generator. 870.4320 Section 870.4320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... of completion of a PDP is required to be filed with the Food and Drug Administration on or...

  8. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass pulsatile flow generator. 870.4320 Section 870.4320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... of completion of a PDP is required to be filed with the Food and Drug Administration on or...

  9. New investigations of a pulsatile impeller blood pump.

    PubMed

    Qian, K X

    1990-01-01

    For circulatory assist devices and total artificial heart systems, impeller blood pumps with small total volumes would be fully implantable. One of the main obstacles, however, is generation of a pulsatile flow. The simplest way to overcome this problem is by changing the pump's revolutions per minute (rpm) periodically, but this often results in severe hemolysis. After theoretic analysis, two in vitro models of impeller blood pumps have been devised, producing pulsatile flow with constant rpm. In the first model, the impeller oscillates in an axial direction during constant rotation. The pump is driven by a DC motor (rotating) and a pneumatic device (oscillating). The form of the pulsatile pressure wave depends upon duration and amplitude of the oscillation. With 40% systolic duration and a 50 mm axial amplitude, a 70 mmHg pressure amplitude (170/100) is achieved with a semiphysiologic shape at a flow of 12 L/min. The second model produces a pulsatile flow by differing the gaps between impeller and cap on the inlet pipe. Both the cap and impeller have cone-shaped heads, and impeller oscillations of 1.5-2 mm, for example, results in a pressure pulse of 40 mmHg (150-110) at 7 L/min flow. Results of theoretic analyses have shown that both models create less turbulence in the impeller, with a consequent reduction in blood cell damage as compared to pumps with changing rpms.

  10. Spatial probabilistic pulsatility model for enhancing photoplethysmographic imaging systems

    NASA Astrophysics Data System (ADS)

    Amelard, Robert; Clausi, David A.; Wong, Alexander

    2016-11-01

    Photoplethysmographic imaging (PPGI) is a widefield noncontact biophotonic technology able to remotely monitor cardiovascular function over anatomical areas. Although spatial context can provide insight into physiologically relevant sampling locations, existing PPGI systems rely on coarse spatial averaging with no anatomical priors for assessing arterial pulsatility. Here, we developed a continuous probabilistic pulsatility model for importance-weighted blood pulse waveform extraction. Using a data-driven approach, the model was constructed using a 23 participant sample with a large demographic variability (11/12 female/male, age 11 to 60 years, BMI 16.4 to 35.1 kg·m-2). Using time-synchronized ground-truth blood pulse waveforms, spatial correlation priors were computed and projected into a coaligned importance-weighted Cartesian space. A modified Parzen-Rosenblatt kernel density estimation method was used to compute the continuous resolution-agnostic probabilistic pulsatility model. The model identified locations that consistently exhibited pulsatility across the sample. Blood pulse waveform signals extracted with the model exhibited significantly stronger temporal correlation (W=35,p<0.01) and spectral SNR (W=31,p<0.01) compared to uniform spatial averaging. Heart rate estimation was in strong agreement with true heart rate [r2=0.9619, error (μ,σ)=(0.52,1.69) bpm].

  11. Lutein derived fragments exhibit higher antioxidant and anti-inflammatory properties than lutein in lipopolysaccharide induced inflammation in rats.

    PubMed

    Nidhi, Bhatiwada; Sharavana, Gurunathan; Ramaprasad, Talahalli R; Vallikannan, Baskaran

    2015-02-01

    In the present study, we appraise the anti-inflammatory efficacy of lutein oxidative degradation derivatives mediated through UV-irradiation over lutein in counteracting the inflammation induced by lipopolysaccharide (LPS) in rats (n = 5 per group). UV-irradiated lutein fragments were identified as anhydrolutein (B, C40H54O), 2,6,6-trimethylcyclohexa-1,4-dienylium (M1, C9H13), (2E,4E,6E,8E)-9-(4-hydroxy-2,6,6-trimethylcyclohex-1-1en-1-yl)-3,7-dimethylnona-2,4,6,8-tetraen-1-ylium (M2, C20H29O), 4-[(1E,3E,5E,7E)-3,7,-dimethyldeca-1,3,5,7-tetraen-1-yl]-3,5,5-methylcyclohex-3-en-1-ol (M3, C21H30O) and zeaxanthin (M4, C40H56O) and its isomers as 13'-Z zeaxanthin, 13'-Z lutein, all-trans zeaxanthin, and 9-Z lutein. Induction of inflammation by LPS significantly increased the production of nitrites (3.3 fold in the serum and 2.6 fold in the liver), prostaglandin E2 (26 fold in the serum), and pro-inflammatory cytokines like tumor necrosis factor-α (6.6 fold in the serum), and interleukin-6 (4.8 fold in the serum). Oxidative derivatives of lutein, especially M1, M2 and M3, ameliorated acute inflammation in rats by inhibiting the production of nitrites, malondialdehyde (MDA), PGE2, TNF-α, and IL-6 cytokines more efficiently than lutein in rats. The anti-inflammatory mechanism of derivatives might be related to the decrease of inflammatory cytokines and the increase of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione S transferase, glutathione reductase), which would result in the reduction of iNOS, COX-2 and MDA and subsequently inflammatory responses.

  12. Lutein recovery from Chlorella sp. ESP-6 with coagulants.

    PubMed

    Utomo, Rhesa Pramudita; Chang, Yin-Ru; Lee, Duu-Jong; Chang, Jo-Shu

    2013-07-01

    Production of algal lutein included cell cultivation, biomass harvesting, cell wall disruption, and subsequent purification if needed. This work cultivated Chlorella sp. ESP-6 cells in photobioreactor to a biomass content of 1.1 gl(-1) and then the freezing-grinding, ultrasonic treatment (20 and 42kHz) and microwave treatment were used to disrupt the cell walls for recover intracellular lutein. The grinding recovered more lutein than ultrasound or microwave pretreatment. Single coagulation using >30 mgl(-1) chitosan or dual-conditioning using 10 mg l(-1) polyaluminum chloride and 10 mgl(-1) chitosan effectively enhance sedimentation and membrane filtration efficiency of algal suspensions. However, the presence of coagulants lowers the lutein yield from algal biomass in the subsequent 20 kHz ultrasound treatment and purification process. Simulation results revealed affine adsorption of lutein onto chitosan molecules via hydroxyl-amine interaction. The possible drawback by pre-treatment stage should be considered together with the subsequent recovery stage in whole process assessment.

  13. The Role of Lutein in Eye-Related Disease

    PubMed Central

    Koushan, Keyvan; Rusovici, Raluca; Li, Wenhua; Ferguson, Lee R.; Chalam, Kakarla V.

    2013-01-01

    The lens and retina of the human eye are exposed constantly to light and oxygen. In situ phototransduction and oxidative phosphorylation within photoreceptors produces a high level of phototoxic and oxidative related stress. Within the eye, the carotenoids lutein and zeaxanthin are present in high concentrations in contrast to other human tissues. We discuss the role of lutein and zeaxanthin in ameliorating light and oxygen damage, and preventing age-related cellular and tissue deterioration in the eye. Epidemiologic research shows an inverse association between levels of lutein and zeaxanthin in eye tissues and age related degenerative diseases such as macular degeneration (AMD) and cataracts. We examine the role of these carotenoids as blockers of blue-light damage and quenchers of oxygen free radicals. This article provides a review of possible mechanisms of lutein action at a cellular and molecular level. Our review offers insight into current clinical trials and experimental animal studies involving lutein, and possible role of nutritional intervention in common ocular diseases that cause blindness. PMID:23698168

  14. Hormonal Perturbations in Occupationally Exposed Nickel Workers

    PubMed Central

    Beshir, Safia; Ibrahim, Khadiga Salah; Shaheen, Weam; Shahy, Eman M.

    2016-01-01

    BACKGROUND: Nickel exposure is recognized as an endocrine disruptor because of its adverse effects on reproduction. AIM: This study was designed to investigate the possible testiculo-hormonal perturbations on workers occupationally exposed to nickel and to assess its effects on human male sexual function. METHODS: Cross-sectional comparative study, comprising 105 electroplating male non-smoker, non-alcoholic workers exposed to soluble nickel and 60 controls was done. Serum luteinizing hormone, follicle stimulating hormone, testosterone levels and urinary nickel concentrations were determined for the studied groups. RESULTS: Serum luteinizing hormone, follicle stimulating hormone, urinary nickel and the simultaneous incidence of more than one sexual disorder were significantly higher in the exposed workers compared to controls. The occurrence of various types of sexual disorders (decreased libido, impotence and premature ejaculation) in the exposed workers was 9.5, 5.1 and 4.4 folds respectively than the controls. CONCLUSIONS: Exposure to nickel produces possible testiculo-hormonal perturbations in those exposed workers. PMID:27335607

  15. Regulation of the Immune System by Hypothalamic Releasing Hormones.

    DTIC Science & Technology

    1987-11-01

    Meyer, W.J. 1987. Decreased mononuclear leukocyte TSH secretion in patients with major depression. Abstr. Society for Neuroscience. 14. Smith, E.M...corticotropin (ACTH). Also, presented are results that the hypothalamic releasing hormones for luteinizing hormone (LH) and thyrotropin ( TSH ) induce...lymphocytes to synthesize immunoreactive LH and TSH , respectively. Finally, we discuss our data that the ACTH receptor on lymphoeytes acts through

  16. Induction of chemokines and prostaglandin synthesis pathways in luteinized human granulosa cells: potential role of luteotropin withdrawal and prostaglandin F2α in regression of the human corpus luteum.

    PubMed

    Luo, Wenxiang; Salih, Sana M; Bormann, Charles L; Wiltbank, Milo C

    2015-12-01

    Our objective was to determine the effects of prostaglandin F2α (PGF2α) and withdrawal of luteotropic stimulants (forskolin or hCG) on expression of chemokines and prostaglandin-endoperoxide synthase 2 (PTGS2) in luteinized human granulosa cells. Human granulosa cells were collected from 12 women undergoing oocyte retrieval and were luteinized in vitro with forskolin or hCG. In first experiment, granulosa-lutein cells were treated with PGF2α, the primary luteolytic hormone in most species. In second experiment, granulosa cells that had been luteinized for 8 d had luteotropins withdrawn for 1, 2, or 3 d. Treatment with PGF2α induced mRNA for chemokine (c-x-c motif) ligand 2 (CXCL2) and CXC ligand 8 (CXCL8; also known as interleukin-8) in granulosa cells luteinized for 8 d but not in cells that were only luteinized for 2 d. Similarly, luteinization of human granulosa cells for 8 d with forskolin or hCG followed by withdrawal of luteotropic stimulants, not only decreased P4 production, but also increased mRNA concentrations for CXCL8, CXCL-2 (after forskolin withdrawal), and PTGS2. These results provide evidence for two key steps in differentiation of luteolytic capability in human granulosa cells. During 8 d of luteinization, granulosa cells acquire the ability to respond to luteolytic factors, such as PGF2α, with induction of genes involved in immune function and PG synthesis. Finally, a decline in luteotropic stimuli triggers similar pathways leading to induction of PTGS2 and possibly intraluteal PGF2α production, chemokine expression, leukocyte infiltration and activation, and ultimately luteal regression.

  17. Quantification of Pressure-Flow Waveforms and Selection of Components for the Pulsatile Extracorporeal Circuit

    PubMed Central

    Wang, Shigang; Haines, Nikkole; Ündar, Akif

    2009-01-01

    Abstract: The debate on pulsatile flow during cardiopulmonary bypass (CPB) has continued for more than half a century. This longstanding debate stems from imprecise quantification methods for arterial pressure and pump flow waveforms and the inability to determine which waveforms accurately depict pulsatile flow. The differences in in vitro and in vivo research outcomes for pulsatile and non-pulsatile flow experiments compounds these issues. The concepts of energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) have been introduced in studies using pulsatile and nonpulsatile flow. Their main advantage lies in their focus on energy gradients rather than pressure gradients as the driving force of blood flow. These formulas can precisely quantify different levels of pulsatility and non-pulsatility, allowing direct and meaningful comparisons. In clinical practice, before using pulsatile flow during CPB, all components of CPB circuits, including the roller pump, membrane oxygenator, arterial filter, aortic cannula, and circuit tubing, should be carefully selected to ensure maximal pulsatility. In addition, it is necessary to select appropriate patients and durations for pulsatile perfusion to obtain better clinical effects. We hope results from our previous experiments can be used as a source of reference when using pulsatile flow in pediatric cardiac surgery. PMID:19361036

  18. Lutein supplementation increases breast milk and plasma lutein concentrations in lactating women and infant plasma concentrations but does not affect other carotenoids.

    PubMed

    Sherry, Christina L; Oliver, Jeffery S; Renzi, Lisa M; Marriage, Barbara J

    2014-08-01

    Lutein is a carotenoid that varies in breast milk depending on maternal intake. Data are lacking with regard to the effect of dietary lutein supplementation on breast milk lutein concentration during lactation and subsequent plasma lutein concentration in breast-fed infants. This study was conducted to determine the impact of lutein supplementation in the breast milk and plasma of lactating women and in the plasma of breast-fed infants 2-3 mo postpartum. Lutein is the dominant carotenoid in the infant brain and the major carotenoid found in the retina of the eye. Eighty-nine lactating women 4-6 wk postpartum were randomly assigned to be administered either 0 mg/d of lutein (placebo), 6 mg/d of lutein (low-dose), or 12 mg/d of lutein (high-dose). The supplements were consumed for 6 wk while mothers followed their usual diets. Breast milk carotenoids were measured weekly by HPLC, and maternal plasma carotenoid concentrations were measured at the beginning and end of the study. Infant plasma carotenoid concentrations were assessed at the end of the study. No significant differences were found between dietary lutein + zeaxanthin intake and carotenoid concentrations in breast milk and plasma or body mass index at baseline. Total lutein + zeaxanthin concentrations were greater in the low- and high-dose-supplemented groups than in the placebo group in breast milk (140% and 250%, respectively; P < 0.0001), maternal plasma (170% and 250%, respectively; P < 0.0001), and infant plasma (180% and 330%, respectively; P < 0.05). Lutein supplementation did not affect other carotenoids in lactating women or their infants. Lactating women are highly responsive to lutein supplementation, which affects plasma lutein concentrations in the infant. This trial was registered at clinicaltrials.gov as NCT01747668.

  19. Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan.

    PubMed

    Johnson, Elizabeth J

    2014-09-01

    The relationship between lutein and zeaxanthin and visual and cognitive health throughout the lifespan is compelling. There is a variety of evidence to support a role for lutein and zeaxanthin in vision. Lutein's role in cognition has only recently been considered. Lutein and its isomer, zeaxanthin, are taken up selectively into eye tissue. Lutein is the predominant carotenoid in human brain tissue. Lutein and zeaxanthin in neural tissue may have biological effects that include antioxidation, anti-inflammation, and structural actions. In addition, lutein and zeaxanthin may be protective against eye disease because they absorb damaging blue light that enters the eye. In pediatric brains, the relative contribution of lutein to the total carotenoids is twice that found in adults, accounting for more than half the concentration of total carotenoids. The greater proportion of lutein in the pediatric brain suggests a need for lutein during neural development as well. In adults, higher lutein status is related to better cognitive performance, and lutein supplementation improves cognition. The evidence to date warrants further investigation into the role of lutein and zeaxanthin in visual and cognitive health throughout the lifespan.

  20. Relationship between lutein and mycotoxin content in durum wheat.

    PubMed

    Delgado, Rosa M; Sulyok, Michael; Jirsa, Ondřej; Spitzer, Tomáš; Krska, Rudolf; Polišenská, Ivana

    2014-01-01

    Levels of lutein and a number of mycotoxins were determined in seven varieties of durum wheat (Triticum durum) and two varieties of common wheat (Triticum aestivum) in order to explore possible relationships amongst these components. Durum wheat cultivars always showed both higher lutein and mycotoxin contents than common wheat cultivars. The mycotoxins detected in both common and durum wheat cultivars were produced by the genera Fusarium, Claviceps, Alternaria and Aspergillus. Fusarium was the major producer of mycotoxins (26 mycotoxins) followed by Claviceps (14 mycotoxins), which was present only in some cultivars such as Chevalier (common wheat), Lupidur and Selyemdur (both durum wheat), Alternaria (six mycotoxins) and Aspergillus (three mycotoxins). Positive correlations between the levels of lutein and mycotoxins in durum wheat cultivars were found for the following mycotoxins: deoxynivalenol (DON), its derivative DON-3-glucoside, moniliformin, culmorin and its derivatives (5-hydroxyculmorin and 15-hydroxyculmorin).

  1. Vitreoscilla hemoglobin gene ( vgb) improves lutein production in Chlorella vulgaris

    NASA Astrophysics Data System (ADS)

    Ma, Ruijuan; Lin, Xiangzhi

    2014-03-01

    Vitreoscilla hemoglobin is an oxygen-binding protein that promotes oxygen delivery and reduces oxygen consumption under low oxygen conditions to increase the efficiency of cell respiration and metabolism. In this study, we introduced a Vitreoscilla hemoglobin gene ( vgb) into Chlorella vulgaris by Agrobacterium tumefaciens -mediated transformation (ATMT). PCR analysis confirmed that the vgb gene was successfully integrated into the Chlorella vulgaris genome. Analysis of biomass obtained in shake flasks revealed transformant biomass concentrations as high as 3.28 g/L, which was 38.81% higher than that of the wild-type strain. Lutein content of transformants also increased slightly. Further experiments recovered a maximum lutein yield of 2.91 mg/L from the transformants, which was 36.77% higher than that of the wild-type strain. The above results suggest that integrated expression of the vgb gene may improve cell growth and lutein yield in Chlorella vulgaris, with applications to lutein production from Chlorella during fermentation.

  2. Recent advances in pulsatile oral drug delivery systems.

    PubMed

    Politis, Stavros N; Rekkas, Dimitrios M

    2013-08-01

    It is well established that several diseases exhibit circadian behavior, following the relevant rhythm of the physiological functions of the human body. Their study falls in the fields of chronobiology and chronotherapeutics, the latter being essentially the effort of timely matching the treatment with the disease expression, in order to maximize the therapeutic benefits and minimize side effects. Pulsatile drug delivery is one of the pillars of chronopharmaceutics, achieved through dosage form design that allows programmable release of active pharmaceutical ingredients (APIs) to follow the disease's time profile. Its major characteristic is the presence of lag phases, followed by drug release in a variety of rates, immediate, repeated or controlled. The scope of this review is to summarize the recent literature on pulsatile oral drug delivery systems and provide an overview of the ready to use solutions and early stage technologies, focusing on the awarded and pending patents in this technical field during the last few years.

  3. Tissue pulsatility imaging of cerebral vasoreactivity during hyperventilation.

    PubMed

    Kucewicz, John C; Dunmire, Barbrina; Giardino, Nicholas D; Leotta, Daniel F; Paun, Marla; Dager, Stephen R; Beach, Kirk W

    2008-08-01

    Tissue pulsatility imaging (TPI) is an ultrasonic technique that is being developed at the University of Washington to measure tissue displacement or strain as a result of blood flow over the cardiac and respiratory cycles. This technique is based in principle on plethysmography, an older nonultrasound technology for measuring expansion of a whole limb or body part due to perfusion. TPI adapts tissue Doppler signal processing methods to measure the "plethysmographic" signal from hundreds or thousands of sample volumes in an ultrasound image plane. This paper presents a feasibility study to determine if TPI can be used to assess cerebral vasoreactivity. Ultrasound data were collected transcranially through the temporal acoustic window from four subjects before, during and after voluntary hyperventilation. In each subject, decreases in tissue pulsatility during hyperventilation were observed that were statistically correlated with the subject's end-tidal CO2 measurements. (

  4. Pulsatile compression of the rostral ventrolateral medulla in hypertension.

    PubMed

    Morimoto, S; Sasaki, S; Miki, S; Kawa, T; Itoh, H; Nakata, T; Takeda, K; Nakagawa, M; Naruse, S; Maeda, T

    1997-01-01

    The rostral ventrolateral medulla (RVLM) has been known to be a major regulating center of sympathetic and cardiovascular activities. An association between essential hypertension and neurovascular compression of the RVLM has been reported in clinical observations, including magnetic resonance imaging (MRI) studies. To reconfirm this relationship, we performed MRI using a high-resolution 512 x 512 matrix in patients with essential and secondary hypertension and in normotensive subjects. The duration of hypertension and the degree of organ damage by hypertension were not significantly different between the two hypertension groups. Neurovascular compression of the RVLM was observed in 74% of the essential hypertension group, and the incidence of compression was significantly higher than in the secondary hypertension group (11%) or in the normotensive group (13%) (P < .01). These results from the clinical studies suggest that neurovascular compression of the RVLM is, at least in part, causally related to essential hypertension. Although blood pressure elevation by pulsatile compression of the RVLM in an experimental baboon model has already been reported, its underlying mechanism is not well known. Accordingly, we performed experiments to investigate whether pulsatile compression of the RVLM would increase arterial pressure and to elucidate the mechanism of the pressor response in rats. Sympathetic nerve activity, arterial pressure, heart rate, and plasma levels of epinephrine and norepinephrine were increased by pulsatile compression of the RVLM. The pressor response was abolished by intravenous treatment with hexamethonium or RVLM injection of kainic acid. In summary, the results from the MRI studies suggest that neurovascular compression of the RVLM is, at least in part, causally related to essential hypertension. This was supported by the results from experimental studies using rats indicating that pulsatile compression of the RVLM increases arterial pressure by

  5. Pulsatility role in cylinder flow dynamics at low Reynolds number

    NASA Astrophysics Data System (ADS)

    Qamar, Adnan; Samtaney, Ravi; Bull, Joseph L.

    2012-08-01

    We present dynamics of pulsatile flow past a stationary cylinder characterized by three non-dimensional parameters: the Reynolds number (Re), non-dimensional amplitude (A) of the pulsatile flow velocity, and Keulegan-Carpenter number (KC = Uo/Dωc). This work is motivated by the development of total artificial lungs (TAL) device, which is envisioned to provide ambulatory support to patients. Results are presented for 0.2 ≤ A ≤ 0.6 and 0.57 ≤ KC ≤ 2 at Re = 5 and 10, which correspond to the operating range of TAL. Two distinct fluid regimes are identified. In both regimes, the size of the separated zone is much greater than the uniform flow case, the onset of separation is function of KC, and the separation vortex collapses rapidly during the last fraction of the pulsatile cycle. The vortex size is independent of KC, but with an exponential dependency on A. In regime I, the separation point remains attached to the cylinder surface. In regime II, the separation point migrates upstream of the cylinder. Two distinct vortex collapse mechanisms are observed. For A < 0.4 and all KC and Re values, collapse occurs on the cylinder surface, whereas for A > 0.4 the separation vortex detaches from the cylinder surface and collapses at a certain distance downstream of the cylinder. The average drag coefficient is found to be independent of A and KC, and depends only on Re. However, for A > 0.4, for a fraction of the pulsatile cycle, the instantaneous drag coefficient is negative indicating a thrust production.

  6. Orbital reconstruction for pulsatile exophthalmos secondary to sphenoid wing dysplasia.

    PubMed

    Dale, Elizabeth L; Strait, Timothy A; Sargent, Larry A

    2014-01-01

    Sphenoid wing dysplasia or absence of the greater sphenoid wing is a rare condition that is considered pathopneumonic for neurofibromatosis type 1 (NF1). It occurs in 4% to 11% of NF1 patients, and its precise cause is unclear. Some cases appear to be congenital, while others have demonstrated it to be a progressive degeneration of the orbital wall. In about half of cases, associated adjacent neurofibromas are described. Consistently, however, the clinical sequelae is herniation of the temporal lobe into the orbit, causing progressive proptosis and pulsatile exophthalmos. Reconstruction of the orbit has traditionally been with bone grafts, but due to problems with bone resorption and recurrence, titanium plates in conjunction with bone grafts have been reported. We present a case of a 6-year-old male patient who was first diagnosed with NF1 and associated absence of the greater sphenoid wing at the age of 2. Four years later, he was referred for reconstruction after the development of pulsatile exophthalmos. Surgical management included dissection of the dura of the temporal lobe off of the periorbita and skull base reconstruction with a combination of radial-shaped titanium mesh and split calvarial bone grafts. Postoperatively, there was near immediate resolution of the pulsatile exophthalmos, and follow-up at 1 year showed no recurrence.

  7. Visualization of pulsatile flow for magnetic nanoparticle based therapies

    NASA Astrophysics Data System (ADS)

    Wentzel, Andrew; Yecko, Philip

    2015-11-01

    Pulsatile flow of blood through branched, curved, stenosed, dilated or otherwise perturbed vessels is more complex than flow through a straight, uniform and rigid tube. In some magnetic hyperthermia and magnetic chemo-therapies, localized regions of magnetic nanoparticle laden fluid are deliberately formed in blood vessels and held in place by magnetic fields. The effect of localized magnetic fluid regions on blood flow and the effect of the pulsatile blood flow on such magnetic fluid regions are poorly understood and difficult to examine in vivo or by numerical simulation. We present a laboratory model that facilitates both dye tracer and particle imaging velocimetry (PIV) studies of pulsatile flow of water through semi-flexible tubes in the presence of localized magnetic fluid regions. Results on the visualization of flows over a range of Reynolds and Womersley numbers and for several different (water-based) ferrofluids are compared for straight and curved vessels and for different magnetic localization strategies. These results can guide the design of improved magnetic cancer therapies. Support from the William H. Sandholm Program of Cooper Union's Kanbar Center for Biomedical Engineering is gratefully acknowledged.

  8. Large-Eddy simulation of pulsatile blood flow.

    PubMed

    Paul, Manosh C; Mamun Molla, Md; Roditi, Giles

    2009-01-01

    Large-Eddy simulation (LES) is performed to study pulsatile blood flow through a 3D model of arterial stenosis. The model is chosen as a simple channel with a biological type stenosis formed on the top wall. A sinusoidal non-additive type pulsation is assumed at the inlet of the model to generate time dependent oscillating flow in the channel and the Reynolds number of 1200, based on the channel height and the bulk velocity, is chosen in the simulations. We investigate in detail the transition-to-turbulent phenomena of the non-additive pulsatile blood flow downstream of the stenosis. Results show that the high level of flow recirculation associated with complex patterns of transient blood flow have a significant contribution to the generation of the turbulent fluctuations found in the post-stenosis region. The importance of using LES in modelling pulsatile blood flow is also assessed in the paper through the prediction of its sub-grid scale contributions. In addition, some important results of the flow physics are achieved from the simulations, these are presented in the paper in terms of blood flow velocity, pressure distribution, vortices, shear stress, turbulent fluctuations and energy spectra, along with their importance to the relevant medical pathophysiology.

  9. Effect of ultrasonic waves on the stability of all-trans lutein and its degradation kinetics.

    PubMed

    Song, Jiang-Feng; Li, Da-Jing; Pang, Hui-Li; Liu, Chun-Quan

    2015-11-01

    Ultrasound treatment has been widely applied in the extraction of biologically active compounds including carotenoids. However, there are few reports on their effects on the stability of these compounds. In the present study, the stability of all-trans lutein, one of the carotenoids, was investigated under the action of ultrasound. Results showed that ultrasound induced the isomerization of all-trans lutein to its isomers, namely to 13-cis lutein, 13'-cis lutein, 9-cis lutein and 9'-cis lutein as analyzed by HPLC coupled with DAD and LC-MS; and the percentage of the isomerization increased with increasing both ultrasonic frequency and power. The stability of all-trans lutein in dichloromethane was worst among multiple kinds of solvents. Interestingly, the retention rate of all-trans lutein improved as the temperature increased, which runs counter to the Arrhenius law. Under ultrasound irradiation, the degradation mechanism might be different with various temperatures, the degradation of all-trans lutein followed first-order kinetics at 20°C, while second-order kinetics was followed at 30-50°C. As the ultrasonic reaction time prolonged, lutein epoxidation nearly occurred. Those results presented here emphasized that UAE techniques should be carefully used in the extraction of all-trans lutein.

  10. Isolation and purification of lutein from the microalga Chlorella vulgaris by extraction after saponification.

    PubMed

    Li, Hua-Bin; Jiang, Yue; Chen, Feng

    2002-02-27

    A simple and efficient method for the isolation and purification of lutein from the microalga Chlorella vulgaris was developed. Crude lutein was obtained by extraction with dichloromethane from the microalga after saponification. Partition values of lutein in the two-phase system of ethanol-water-dichloromethane at different ratios were measured by HPLC so as to assist the determination of an appropriate condition for washing water-soluble impurities in the crude lutein. Partition values of lutein in another two-phase system of ethanol-water-hexane at different ratios were also measured by HPLC for determining the condition for removing fat-soluble impurities. The water-soluble impurities in the crude lutein were removed by washing with 30% aqueous ethanol, and the fat-soluble impurities were removed by extraction with hexane. The final purity of lutein obtained was 90-98%, and the yield was 85-91%.

  11. Incorporation of lutein and docosahexaenoic acid from dietary microalgae into the retina in quail.

    PubMed

    Schnebelen-Berthier, Coralie; Acar, Niyazi; Pouillart, Philippe; Thabuis, Clementine; Rodriguez, Bertrand; Depeint, Flore; Clerc, Elise; Mathiaud, Adeline; Bourdillon, Anne; Baert, Blandine; Bretillon, Lionel; Lecerf, Jean-Michel

    2015-03-01

    Lutein and docosahexaenoic acid (DHA) are associated with the prevention of age-related macular degeneration (AMD). Since microalgae are potent natural sources of these nutrients, their nutritional value should be evaluated based on the bioavailability of lutein and DHA for the retina via the plasmatic compartment. In this study, quail were fed for 5 months either with a diet supplemented or deprived with microalgae rich in lutein and DHA. In the microalgae-fed group, the retinal concentrations of lutein and zeaxanthin gradually increased whereas in plasma, these compounds started to increase from the first month of supplementation. We also observed a significant increase in retinal and plasmatic levels of DHA in the microalgae-fed group. In conclusion, the plasmatic and retinal contents of lutein and DHA were significantly increased in quail fed with lutein- and DHA-rich microalgae. Food fortification with microalgae may be an innovative way to increase lutein and DHA consumption in humans.

  12. In vitro bioaccessibility and monolayer uptake of lutein from wholegrain baked foods.

    PubMed

    Read, Andrew; Wright, Amanda; Abdel-Aal, El-Sayed M

    2015-05-01

    Lutein-enriched foods would contribute towards promoting the consumption of this important carotenoid. In the current study cookies, muffins, and flatbreads were produced at three enrichment levels (0.5, 1.0 and 2.0mg lutein per serving) to investigate lutein bioavailability in vitro. Foods were subjected to in vitro simulation of human upper gastrointestinal digestion coupled with a Caco-2 monolayer absorption assay. Digestive conditions representative of the fed state conditions associated with significantly higher lutein bioaccessibility compared with the fasted state (p < 0.001). Lutein bioaccessibility of cookies and muffins was higher than flatbreads due to their elevated fat content, measured under either fed or fasted conditions. Lutein concentration in the aqueous phase was the most important factor in determining apical cell uptake of lutein, with cookies and muffins exhibiting a higher lutein uptake than flatbreads (p < 0.05). As commonly consumed foods, lutein-enriched cookies, muffins, and flatbreads have the potential to improve lutein intake.

  13. An optimization formulation for characterization of pulsatile cortisol secretion.

    PubMed

    Faghih, Rose T; Dahleh, Munther A; Brown, Emery N

    2015-01-01

    Cortisol is released to relay information to cells to regulate metabolism and reaction to stress and inflammation. In particular, cortisol is released in the form of pulsatile signals. This low-energy method of signaling seems to be more efficient than continuous signaling. We hypothesize that there is a controller in the anterior pituitary that leads to pulsatile release of cortisol, and propose a mathematical formulation for such controller, which leads to impulse control as opposed to continuous control. We postulate that this controller is minimizing the number of secretory events that result in cortisol secretion, which is a way of minimizing the energy required for cortisol secretion; this controller maintains the blood cortisol levels within a specific circadian range while complying with the first order dynamics underlying cortisol secretion. We use an ℓ0-norm cost function for this controller, and solve a reweighed ℓ1-norm minimization algorithm for obtaining the solution to this optimization problem. We use four examples to illustrate the performance of this approach: (i) a toy problem that achieves impulse control, (ii) two examples that achieve physiologically plausible pulsatile cortisol release, (iii) an example where the number of pulses is not within the physiologically plausible range for healthy subjects while the cortisol levels are within the desired range. This novel approach results in impulse control where the impulses and the obtained blood cortisol levels have a circadian rhythm and an ultradian rhythm that are in agreement with the known physiology of cortisol secretion. The proposed formulation is a first step in developing intermittent controllers for curing cortisol deficiency. This type of bio-inspired pulse controllers can be employed for designing non-continuous controllers in brain-machine interface design for neuroscience applications.

  14. Pulsatile flow and mass transport past a circular cylinder

    NASA Astrophysics Data System (ADS)

    Zierenberg, Jennifer R.; Fujioka, Hideki; Suresh, Vinod; Bartlett, Robert H.; Hirschl, Ronald B.; Grotberg, James B.

    2006-01-01

    The mass transport of a pulsatile free-stream flow past a single circular cylinder is investigated as a building block for an artificial lung device. The free stream far from the cylinder is represented by a time-periodic (sinusoidal) component superimposed on a steady velocity. The dimensionless parameters of interest are the steady Reynolds number (Re), Womersley parameter (α), sinusoidal amplitude (A), and the Schmidt number (Sc). The ranges investigated in this study are 5⩽Re⩽40, 0.25⩽α⩽4, 0.25⩽A⩽0.75, and Sc =1000. A pair of vortices downstream of the cylinder is observed in almost all cases investigated. These vortices oscillate in size and strength as α and A are varied. For α <αc, where αc=0.005A-1.13Re1.33, the vortex is always attached to the cylinder (persistent); while for α >αc, the vortex is attached to the cylinder only during part of a time cycle (intermittent). The time-averaged Sherwood number, Sh̿, is found to be largely influenced by the steady Reynolds number, increasing approximately as Re1/2. For α =0.25, Sh̿ is less than the steady (α =0, A =0) value and decreases with increasing A. For α =2 and α =4, Sh̿ is greater than the steady value and increases with increasing A. These qualitatively opposite effects of pulsatility are discussed in terms of quasisteady versus unsteady transport. The maximum increase over steady transport due to pulsatility varies between 14.4% and 20.9% for Re =10-40, α =4, and A =0.75.

  15. The importance of flow pulsatility for the rate of transvascular fluid filtration in lungs.

    PubMed

    Hauge, A; Nicolaysen, G

    1979-05-01

    1. The rate of transvascular fluid filtration has been studied with a gravimetric technique in isolated perfused rabbit lungs during periods of elevated left atrial pressure (PLA). 2. Fluid filtration was expressed as the filtration coefficient, Kf (g/min x 100 g bloodless lung x mmHg PLA) and determined during alternately pulsatile and non-pulsatile perfusion in six zone III and three zone II/I lung preparations. Perfusion pattern was changed without interruption of flow. Mean in- and outflow pressures were kept constant. 3. In all the lungs it was found that Kf was higher during pulsatile than during non-pulsatile flow (P less than 0.01). Mean Kf (+/- S.E. of mean) for the zone III preparations was 0.42 (+/- 0.089) and 0.27 (+/- 0.057) for pulsatile and non-pulsatile perfusion, respectively. The corresponding figures for the zone II/I preparations were 0.11 (+/- 0.035) and 0.04 (+/- 0.030). 4. We suggest that the difference is due to a larger filtration area and/or a higher mean microvascular hydrostatic pressure during pulsatile than during non-pulsatile flow and not to a rise in hydraulic conductivity due to pressure pulsations ('stretched pores'). 5. When the water-exchange function of the lung is considered, flow pattern should be taken into account as an entity in its own right in addition to the steady state or the mean component of blood flow.

  16. Dietary lutein modulates growth and survival genes in prostate cancer cells.

    PubMed

    Rafi, Mohamed M; Kanakasabai, Saravanan; Gokarn, Sarita V; Krueger, Eric G; Bright, John J

    2015-02-01

    Lutein is a carotenoid pigment present in fruits and vegetables that has anti-inflammatory and antitumor properties. In this study, we examined the effect of lutein on proliferation and survival-associated genes in prostate cancer (PC-3) cells. We found that in vitro culture of PC-3 cells with lutein induced mild decrease in proliferation that improved in combination treatment with peroxisome proliferator-activated receptor gamma (PPARγ) agonists and other chemotherapeutic agents. Flow cytometry analyses showed that lutein improved drug-induced cell cycle arrest and apoptosis in prostate cancer. Gene array and quantitative reverse transcription-polymerase chain reaction analyses showed that lutein altered the expression of growth and apoptosis-associated biomarker genes in PC-3 cells. These findings highlight that lutein modulates the expression of growth and survival-associated genes in prostate cancer cells.

  17. Determination of Lutein from Fruit and Vegetables Through an Alkaline Hydrolysis Extraction Method and HPLC Analysis.

    PubMed

    Fratianni, Alessandra; Mignogna, Rossella; Niro, Serena; Panfili, Gianfranco

    2015-12-01

    A simple and rapid analytical method for the determination of lutein content, successfully used for cereal matrices, was evaluated in fruit and vegetables. The method involved the determination of lutein after an alkaline hydrolysis of the sample matrix, followed by extraction with solvents and analysis by normal phase HPLC. The optimized method was simple, precise, and accurate and it was characterized by few steps that could prevent loss of lutein and its degradation. The optimized method was used to evaluate the lutein amounts in several fruit and vegetables. Rich sources of lutein were confirmed to be green vegetables such as parsley, spinach, chicory, chard, broccoli, courgette, and peas, even if in a range of variability. Taking into account the suggested reference values these vegetables can be stated as good sources of lutein.

  18. Microwave-assisted hydrolysis of lutein and zeaxanthin esters in marigold (Tagetes erecta L.).

    PubMed

    Liu, Hongcheng; Zhang, Ying; Zheng, Bin; Li, Qiwan; Zou, Yanhong

    2011-12-01

    Saponification of lutein and zeaxanthin was performed by microwave-assisted hydrolysis (MAH) and analysed by ultra performance liquid chromatography. The optimal condition of MAH was studied, and the degradation or isomerization of lutein and zeaxanthin were estimated under MAH. The concentrations of lutein and zeaxanthin in 20 marigold samples were assessed by saponification using traditional heater and MAH, the regression coefficient of lutein obtained by two methods was 0.9688 and that of zeaxanthin was 0.9527. The limit of detection for lutein and zeaxanthin was 0.05 and 0.1 μg/ml, respectively, and the limit of quantification for lutein and zeaxanthin was 0.05 mg/100 g and 0.1 mg/100 g, respectively.

  19. Expression of the putative gonadotropin-inhibitory hormone receptor, NPFFR1, in the anterior pituitary gland of the gilt is affected by age and sexual maturation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gonadotropin-inhibitory hormone (GnIH) purportedly suppresses secretion of luteinizing hormone (LH) by acting through a G-protein coupled receptor (NPFFR1) in the anterior pituitary gland and hypothalamus. The objective of these studies was to determine if expression of mRNA for NPFFR1 in the reprod...

  20. Fluid-structure interaction for nonlinear response of shells conveying pulsatile flow

    NASA Astrophysics Data System (ADS)

    Tubaldi, Eleonora; Amabili, Marco; Païdoussis, Michael P.

    2016-06-01

    Circular cylindrical shells with flexible boundary conditions conveying pulsatile flow and subjected to pulsatile pressure are investigated. The equations of motion are obtained based on the nonlinear Novozhilov shell theory via Lagrangian approach. The flow is set in motion by a pulsatile pressure gradient. The fluid is modeled as a Newtonian pulsatile flow and it is formulated using a hybrid model that contains the unsteady effects obtained from the linear potential flow theory and the pulsatile viscous effects obtained from the unsteady time-averaged Navier-Stokes equations. A numerical bifurcation analysis employs a refined reduced order model to investigate the dynamic behavior. The case of shells containing quiescent fluid subjected to the action of a pulsatile transmural pressure is also addressed. Geometrically nonlinear vibration response to pulsatile flow and transmural pressure are here presented via frequency-response curves and time histories. The vibrations involving both a driven mode and a companion mode, which appear due to the axial symmetry, are also investigated. This theoretical framework represents a pioneering study that could be of great interest for biomedical applications. In particular, in the future, a more refined model of the one here presented will possibly be applied to reproduce the dynamic behavior of vascular prostheses used for repairing and replacing damaged and diseased thoracic aorta in cases of aneurysm, dissection or coarctation. For this purpose, a pulsatile time-dependent blood flow model is here considered by applying physiological waveforms of velocity and pressure during the heart beating period. This study provides, for the first time in literature, a fully coupled fluid-structure interaction model with deep insights in the nonlinear vibrations of circular cylindrical shells subjected to pulsatile pressure and pulsatile flow.

  1. Prediction and control of neural responses to pulsatile electrical stimulation.

    PubMed

    Campbell, Luke J; Sly, David James; O'Leary, Stephen John

    2012-04-01

    This paper aims to predict and control the probability of firing of a neuron in response to pulsatile electrical stimulation of the type delivered by neural prostheses such as the cochlear implant, bionic eye or in deep brain stimulation. Using the cochlear implant as a model, we developed an efficient computational model that predicts the responses of auditory nerve fibers to electrical stimulation and evaluated the model's accuracy by comparing the model output with pooled responses from a group of guinea pig auditory nerve fibers. It was found that the model accurately predicted the changes in neural firing probability over time to constant and variable amplitude electrical pulse trains, including speech-derived signals, delivered at rates up to 889 pulses s(-1). A simplified version of the model that did not incorporate adaptation was used to adaptively predict, within its limitations, the pulsatile electrical stimulus required to cause a desired response from neurons up to 250 pulses s(-1). Future stimulation strategies for cochlear implants and other neural prostheses may be enhanced using similar models that account for the way that neural responses are altered by previous stimulation.

  2. Cinematics and sticking of heart valves in pulsatile flow test.

    PubMed

    Köhler, J; Wirtz, R

    1991-05-01

    The aim of the project was to develop laboratory test devices for studies of the cinematics and sticking behaviour of technical valve protheses. The second step includes testing technical valves of different types and sizes under static and dynamic conditions. A force-deflection balance was developed in order to load valve rims by static radial forces until sticking or loss of a disc (sticking- and clamping-mould point) with computer-controlled force deflection curves. A second deflection device was developed and used for prosthetic valves in the aortic position of a pulsatile mock circulation loop with simultaneous video-cinematography. The stiffness of technical valve rims varied between 0.20 (St. Jude) and about 1.0 N/micron (metal rim valves). The stiffness decreased significantly with increasing valve size. Sticking under pulsatile flow conditions was in good agreement with the static deflection measurements. Hence, valve sticking with increasing danger of thrombus formation is more likely with a less stiff valve rim. In the case of forces acting perpendicularly to the pendulum axis, the clamping mould-point of the valve can be reached, followed by disc dislodgement.

  3. [Five years experience with non-pulsatile flow].

    PubMed

    Grinda, J M; Bricourt, M O; Salvi, S; Jouan, J; Guillemain, R; Deloche, A; Fabiani, J N

    2005-10-01

    Mechanical circulatory assistances now belong to the therapeutic stock in case of advanced heart failure. Their mainspring lays on the substitution of the failing left and/or right ventricle function with a pump. The goal being to maintain or restore the system main functions. Their main indication is a bridge to transplant mechanical circulatory assistance, allowing the patient to await transplantation. However, indications for definitive implantation appear in case of transplantation counter indication, mechanical circulatory assistances already emerging as a possible alternative to transplantation. For over 10 years, we have used pulsatile flow assistances, either with pneumatic ventricles or electro-mechanic implantable left ventricles. We henceforth observe the development of a new generation of implantable assistance providing a non-pulsatile flow. These are axial pumps. We evaluated the first model, the DeBakey axial pump which became the most used axial pump worldwide. We now observe the development of other axial pumps as well as the development of new implantable centrifugal pumps.

  4. Pulsatile uptake of CO in the human lung

    PubMed Central

    Menkes, Harold A.; Sera, Kazuaki; Rogers, Robert M.; Hyde, Richard W.; Forster, Robert E.; DuBois, Arthur B.

    1970-01-01

    The instantaneous uptake of CO in the lungs was measured with a water-filled body plethysmograph in normal man. First, control measurements of plethysmograph pressure were made while the subject held his breath for 7 sec after breathing gas mixtures prepared to bring his alveolar PO2 and PCO2 close to mixed venous levels. Then, CO uptake measurements were made while he held his breath after inhaling the same gas mixtures with added CO (2.0%). The change in lung volume on CO minus the change in lung volume during the control measurement was a measure of the CO uptake in the lungs. Cardiopneumatic changes in lung gas volume were subtracted electrically. All of five subjects showed pulsatile CO uptake. The mean CO uptake was 103 ml/min. A peak uptake of 2.0 (range 1.6-2.3) times the mean uptake occurred 0.3-0.4 sec after the R wave of the EKG and a minimum uptake of 0.4 (range 0.2-0.5) times the mean uptake occurred during the tenth of a second before the R wave of the EKG. These results suggest that pulmonary capillary blood volume is pulsatile during the cardiac cycle. PMID:5411784

  5. Pulsatile ventricular assist device with pericardial inner lining.

    PubMed

    Leirner, A A; Hayashida, S A; Maizato, M J; Silva M de-L; Cestari, I A; Affeld, K

    2001-11-01

    Preserved pericardium in contact with blood is not thrombogenic, therefore avoiding the use of anticoagulants, and has excellent mechanical properties. Our objective is to take advantage of these characteristics and build a pulsatile ventricular assist device (VAD) with pericardium used as the inner lining of the blood chamber. A mold is used for the tanning of the pericardium, rendering it with an exact shape. A flexible polymeric structure is designed to serve as a base for the pericardium, guiding it and limiting its rate of strain. It consists of two halves, which when outfitted with the interior pericardium lining and connected to each other, form the blood chamber. This assembly is housed in rigid polyvinyl chloride (PVC) shells making up the air chamber for the pneumatic activation. Valves are likewise made of pericardium. Sealing of the chambers was tested statically up to 300 mm Hg with no air or fluid leakage. The device was tested for 60 continuous days in a mock loop, demonstrating hydrodynamic performance adequate for ventricular assist. Micrographs (confocal laser and scanning electron microscopy) were obtained of several pericardium areas, especially on the flexing regions that are a transition between the wet and dry regions. No sign of damage to the pericardium was observed either with the naked eye or at the microscopic level. From the hydraulic performance and materials viewpoints, a completely pericardium-lined pulsatile VAD displaying a polymeric structure that avoids unpredictable bending and limits strain is feasible. The results warrant further studies regarding biocompatibility and strength advantages.

  6. Prediction and control of neural responses to pulsatile electrical stimulation

    NASA Astrophysics Data System (ADS)

    Campbell, Luke J.; Sly, David James; O'Leary, Stephen John

    2012-04-01

    This paper aims to predict and control the probability of firing of a neuron in response to pulsatile electrical stimulation of the type delivered by neural prostheses such as the cochlear implant, bionic eye or in deep brain stimulation. Using the cochlear implant as a model, we developed an efficient computational model that predicts the responses of auditory nerve fibers to electrical stimulation and evaluated the model's accuracy by comparing the model output with pooled responses from a group of guinea pig auditory nerve fibers. It was found that the model accurately predicted the changes in neural firing probability over time to constant and variable amplitude electrical pulse trains, including speech-derived signals, delivered at rates up to 889 pulses s-1. A simplified version of the model that did not incorporate adaptation was used to adaptively predict, within its limitations, the pulsatile electrical stimulus required to cause a desired response from neurons up to 250 pulses s-1. Future stimulation strategies for cochlear implants and other neural prostheses may be enhanced using similar models that account for the way that neural responses are altered by previous stimulation.

  7. A model of pulsatile flow in a uniform deformable vessel.

    PubMed

    Johnson, G A; Borovetz, H S; Anderson, J L

    1992-01-01

    Simulations of blood flow in natural and artificial conduits usually require large computers for numerical solution of the Navier-Stokes equations. Often, physical insight into the fluid dynamics is lost when the solution is purely numerical. An alternative to solving the most general form of the Navier-Stokes equations is described here, wherein a functional form of the solution is assumed in order to simplify the required computations. The assumed forms for the axial pressure gradient and velocity profile are chosen such that conservation of mass is satisfied for fully established pulsatile flow in a straight, deformable vessel. The resulting equations are cast in finite-difference form and solved explicitly. Results for the limiting cases of rigid wall and zero applied pressure are found to be in good agreement with analytical solutions. Comparison with the experimental results of Klanchar et al. [Circ. Res. 66, 1624-1635 (1990]) also shows good agreement. Application of the model to realistic physiological parameter values provides insight as to the influence of the pulsatile nature of the flow field on wall shear development in the presence of a moving wall boundary. Specifically, the model illustrates the dependence of flow rate and shear rate on the amplitude of the vessel wall motion and the phase difference between the applied pressure difference and the oscillations of the vessel radius. The present model can serve as a useful tool for experimentalists interested in quantifying the magnitude and character of velocity profiles and shearing forces in natural and artificial biologic conduits.

  8. Lutein Has a Protective Effect on Hepatotoxicity Induced by Arsenic via Nrf2 Signaling

    PubMed Central

    Li, Shugang; Ding, Yusong; Niu, Qiang; Xu, Shangzhi; Pang, Lijuan; Ma, Rulin; Jing, Mingxia; Feng, Gangling; Tang, Jing Xia; Zhang, Qian; Ma, Xiaomei; Yan, Yizhong; Wang, Hai Xia; Li, Feng; Guo, Shuxia

    2015-01-01

    Arsenic produces liver disease through the oxidative stress. While lutein can alleviate cytotoxic and oxidative injury, nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a critical role in defending oxidative species. However, the mechanisms by which lutein protects the liver against the effect of arsenic are not known. Therefore, this study aims to investigate the mechanisms involved in the action of lutein using mice model in which hepatotoxicity was induced by arsenic. We found that mice treatment with lutein could reverse changes in morphological and liver indexes and result in a significant improvement in hepatic function comparing with arsenic trioxide group. Lutein treatment improved the activities of antioxidant enzymes and attenuated increasing of ROS and MDA induced by arsenic trioxide. Lutein could increase the mRNA and protein expression of Nrf2 signaling related genes (Nrf2, Nqo1, Ho-1, and Gst). These findings provide additional evidence that lutein may be useful for reducing reproductive injury associated with oxidative stress by the activation of Nrf2 signaling. Our findings suggest a possible mechanism of antioxidant lutein in preventing the hepatotoxicity, which implicate that a dietary lutein may be a potential treatment for liver diseases, especially for arsenicosis therapy. PMID:25815309

  9. Lutein has a protective effect on hepatotoxicity induced by arsenic via Nrf2 signaling.

    PubMed

    Li, Shugang; Ding, Yusong; Niu, Qiang; Xu, Shangzhi; Pang, Lijuan; Ma, Rulin; Jing, Mingxia; Feng, Gangling; Tang, Jing Xia; Zhang, Qian; Ma, Xiaomei; Yan, Yizhong; Zhang, Jingyu; Wei, Meng; Wang, Hai Xia; Li, Feng; Guo, Shuxia

    2015-01-01

    Arsenic produces liver disease through the oxidative stress. While lutein can alleviate cytotoxic and oxidative injury, nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a critical role in defending oxidative species. However, the mechanisms by which lutein protects the liver against the effect of arsenic are not known. Therefore, this study aims to investigate the mechanisms involved in the action of lutein using mice model in which hepatotoxicity was induced by arsenic. We found that mice treatment with lutein could reverse changes in morphological and liver indexes and result in a significant improvement in hepatic function comparing with arsenic trioxide group. Lutein treatment improved the activities of antioxidant enzymes and attenuated increasing of ROS and MDA induced by arsenic trioxide. Lutein could increase the mRNA and protein expression of Nrf2 signaling related genes (Nrf2, Nqo1, Ho-1, and Gst). These findings provide additional evidence that lutein may be useful for reducing reproductive injury associated with oxidative stress by the activation of Nrf2 signaling. Our findings suggest a possible mechanism of antioxidant lutein in preventing the hepatotoxicity, which implicate that a dietary lutein may be a potential treatment for liver diseases, especially for arsenicosis therapy.

  10. Phase II enzyme induction by a carotenoid, lutein, in a PC12D neuronal cell line

    SciTech Connect

    Miyake, Seiji; Kobayashi, Saori; Tsubota, Kazuo; Ozawa, Yoko

    2014-04-04

    Highlights: • Lutein reduced ROS levels in a PC12D neuronal cell line. • Lutein induced mRNAs of phase II antioxidative enzymes in PC12D neuronal cells. • Lutein increased protein levels of HO-1, SOD2, and NQO-1 in PC12D neuronal cells. • Lutein had no effect on intranuclear Nrf2 levels in PC12D neuronal cells. • Lutein did not activate potential upstream Nrf2 nuclear translocation pathways. - Abstract: The mechanism by which lutein, a carotenoid, acts as an antioxidant in retinal cells is still not fully understood. Here, lutein treatment of a neuronal cell line (PC12D) immediately resulted in reduced intracellular ROS levels, implying that it has a direct role in ROS scavenging. Significantly, lutein treatment also induced phase II antioxidative enzyme expression, probably via a nuclear factor-like 2 (Nrf2) independent pathway. This latter mechanism could explain why lutein acts diversely to protect against oxidative/cytotoxic stress, and why it is physiologically involved in the human neural tissue, such as the retina.

  11. Hormone Therapy

    MedlinePlus

    ... estrogen , a hormone that helps control the menstrual cycle . Changing estrogen levels can bring on symptoms such ... two hormones—estrogen and progesterone —control your menstrual cycle. These hormones are made by the ovaries . Estrogen ...

  12. Persistent Organochlorine Pollutants with Endocrine Activity and Blood Steroid Hormone Levels in Middle-Aged Men

    PubMed Central

    Emeville, Elise; Giton, Frank; Giusti, Arnaud; Oliva, Alejandro; Fiet, Jean; Thomé, Jean-Pierre; Blanchet, Pascal; Multigner, Luc

    2013-01-01

    Background Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results. Objective We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone. Methods We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples. Results DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone. Conclusions These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern

  13. 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.

  14. Hypohydration and Acclimation: Effects on Hormone Responses to Excercise/Heat Stress.

    DTIC Science & Technology

    1983-03-15

    During acclimation and test intervals, Ss wore shorts, t-shirts, and tennis shoes; ad lib water was available during the acclimation regimen, and in... anaerobic exercise on GH while Okada et al. (18) " reported the effects of passive heat exposure. As in our own experiments several earlier studies... anaerobic running exercise on plasma growth hormone, cortisol, luteinizing hormone, testosterone, androstenedione, estrone and estradiol. 3. Ster

  15. Hormone changes triggered by aggression in a natural population of blackbirds.

    PubMed

    Harding, C F; Follett, B K

    1979-03-02

    The concentrations of hormones in the plasma of male red-winged blackbirds caught at the height of an aggressive encounter are significantly different from those in males that have not recently engaged in aggressive behavior. Concentrations of luteinizing hormone in the plasma are decreased in the aggressive males, whereas androgen concentrations are affected in a more complex manner. Concentrations of corticoids do not appear to be affected by aggressive behavior.

  16. Oxidative Stress in Granulosa-Lutein Cells From In Vitro Fertilization Patients.

    PubMed

    Ávila, Julio; González-Fernández, Rebeca; Rotoli, Deborah; Hernández, Jairo; Palumbo, Angela

    2016-12-01

    Ovarian aging is associated with gradual follicular loss by atresia/apoptosis. Increased production of toxic metabolites such as reactive oxygen species (ROS) and reactive nitrogen species as well as external oxidant agents plays an important role in the process of ovarian senescence and in the pathogenesis of ovarian pathologies such as endometriosis and polycystic ovary syndrome (PCOS). This review provides a synthesis of available studies of oxidative stress (OS) in the ovary, focusing on the most recent evidence obtained in mural granulosa-lutein (GL) cells of in vitro fertilization patients. Synthesis of antioxidant enzymes such as peroxiredoxin 4, superoxide dismutase, and catalase and OS damage response proteins such as aldehyde dehydrogenase 3, member A2 decreases with aging in human GL cells, favoring an unbalance in ROS/antioxidants that mediates molecular damage and altered cellular function. The increase in OS in the granulosa cell correlates with diminished expression of follicle-stimulating hormone receptor (FSHR) and a dysregulation of the FSHR signaling pathway and may be implicated in disrupted steroidogenic function and poor response to FSH in women with aging. Women with endometriosis and PCOS have lower antioxidant production capacity that may contribute to abnormal follicular development and infertility. Further investigation of the signaling pathways involved in cellular response to OS could shed light into molecular characterization of these diseases and development of new treatment strategies to improve reproductive potential in these women.

  17. Luteinized unruptured follicle syndrome in mild endometriosis. Assessment with biochemical parameters.

    PubMed

    Holtz, G; Williamson, H O; Mathur, R S; Landgrebe, S C; Moore, E E

    1985-09-01

    Failure to extrude an ovum, with subsequent luteinization of the unruptured follicle (LUF), has been proposed as a cause of infertility in women with mild endometriosis. To assess the incidence of this process we performed laparoscopies in the early luteal phase on 16 women with mild endometriosis and 8 control subjects. Peritoneal fluid was aspirated and a plasma sample obtained concurrently. Estradiol (E2) and progesterone (P) concentrations were determined. A review of the literature suggested that the following hormonal criteria correlated with follicular rupture: fluid E2 greater than or equal to 500 pg/ml, E2 fluid/plasma ratio greater than or equal to 3.1, fluid P greater than or equal to 3,000 ng/dl and P fluid/plasma ratio greater than or equal to 5:1. All control subjects met at least one E2 and one P criterion: 75% met all. In contrast, less than one-third with mild endometriosis met all, and three (19%) met none. Five met only E2 criteria. These findings suggest that LUF occurs occasionally in association with mild endometriosis. Additionally, ovarian steroidogenesis, particularly P secretion, was impaired frequently in the absence of LUF in women with endometriosis.

  18. Association of pulsatile and mean cerebral blood flow velocity with age and neuropsychological performance.

    PubMed

    Pase, Matthew P; Grima, Natalie A; Stough, Con; Scholey, Andrew; Pipingas, Andrew

    2014-05-10

    Low cerebral blood flow velocity is associated with cognitive decline. However, the association between pulsatile brain blood flow velocity and cognition has not been investigated. High pulsatile hemodynamic stress in the brain may impair cognitive function through damage to small cerebral vessels. The current objective was to examine the cross-sectional association of pulsatile and mean cerebral blood flow velocity with age and neuropsychological performance. We also examined whether cerebral blood flow velocity was associated with aortic pulse pressure, a measure of arterial ageing and aortic stiffness. Cerebral blood flow velocity was measured in the middle cerebral artery using Transcranial Doppler Ultrasonography (TDU) while neuropsychological performance was measured using a computerized cognitive test battery. Aortic pulse pressure was non-invasively derived from applanation tonometry of the radial artery. The sample comprised 160 healthy adults aged 50-70 years. Results indicated that increasing age correlated with lower mean (r=-0.23, p<0.01) and higher pulsatile (r=0.27, p<0.01) brain blood flow velocity. In multivariate adjusted models, both peripheral (β=0.28, p<0.05) and aortic (β=0.24, p<0.05) pulse pressure were associated with higher pulsatile flow velocity through the middle cerebral artery. In adjusted models, neither mean nor pulsatile cerebral blood flow velocity was associated with performance on any cognitive task. In conclusion, arterial ageing was associated with increased pulsatile hemodynamic stress in the brain. However, this was not associated with impaired neuropsychological performance.

  19. Study of erythrocyte aggregation at pulsatile flow conditions with backscattering analysis.

    PubMed

    Nam, Jeong-Hun; Xue, Shubin; Lim, Hyunjung; Shin, Sehyun

    2012-01-01

    In vivo red blood cell aggregation will vary under pulsatile flow but few studies have been reported due to various difficulties in generating physiological flow conditions and detecting RBC aggregation. The present study developed a microfluidic system that generates cyclic pulsatile flow through a microchannel. Backscattered light signals from human blood were recorded over time and analyzed for RBC aggregation in pulsatile flow. Four different blood samples (control, normal RBCs in PBS, hardened RBCs in autologous plasma, and hardened RBCs in PBS) were examined. In a cyclic pulsatile flow condition, light intensity-time curve for the control and hardened RBCs in plasma exhibited apparent critical shear stresses that were similar to the respective values measured at a single pulse flow condition. During entire cycles of pulsatile flow, the measured critical shear stress remained nearly constant. We conclude that the critical shear stress can be observed in cyclic pulsatile flow and would be an important index to represent in-vivo pulsatile blood flow rheology.

  20. Mechanics of pulsatile transpyloric flow in the pig.

    PubMed

    Anvari, M; Dent, J; Malbert, C; Jamieson, G G

    1995-10-01

    1. In eight conscious pigs equipped with gastric and duodenal cannulae, the relationship of transpyloric flow to gastro-duodenal motor events was evaluated during gastric emptying of 1000 ml of saline. Rates of liquid gastric emptying were correlated with pressures at the antrum, pylorus and duodenum, recorded by a sleeve sensor and multiple perfused side-holes. Transpyloric flow was recorded concurrently by continuous collection and weighing of the duodenal effluent. 2. In three pigs the above measurements were repeated during concurrent videofluoroscopy of gastric emptying after adding 100 ml of liquid barium to the gastric instillate. 3. The mean volume of saline emptied in 30 min was 627 +/- 51.2 ml. Pulsatile flow accounted for 71% of total emptying. Pulses had a mean flow rate of 3.9 +/- 0.44 ml s-1. Most flow pulses (59%) occurred during the first 5 min of emptying. 4. Distinctive, low-amplitude (4.8 +/- 0.33 mmHg), relatively long-lasting (15.8 +/- 0.46 s) antral pressure waves were associated with 58% of flow pulses. In all antral pressure recording points, the first and longest duration component of these pressure waves had an identical timing, amplitude and waveform consistent with pressurization of the entire antrum-gastric cavity. 5. Videofluoroscopy and concurrent manometry showed that these antral common cavity pressure waves were associated with non-lumen-occlusive contractions of the gastric wall, initially observed at the corpus which propagated down to the pylorus; 93% of these contractions became lumen occlusive in the terminal antrum and pylorus when pressure waves of a unique pattern for each recording point were recorded at this level. 6. The onset of 68% of the flow pulses which accounted for 62% of pulsatile emptying occurred in the interval (mean 7.9 +/- 0.65 s) between the onset of the common cavity wave and the onset of localized, lumen-occlusive distal antral-pyloric pressure waves. 7. These findings indicate that in the pig, pulsatile

  1. Comparison of pumps and oxygenators with pulsatile and nonpulsatile modes in an infant cardiopulmonary bypass model.

    PubMed

    Haines, Nikkole M; Wang, Shigang; Kunselman, Allen; Myers, John L; Undar, Akif

    2009-11-01

    As the evidence mounts in favor of pulsatile perfusion during CPB, it is necessary to investigate the effect of circuit components on the quality of pulsatility delivered throughout the circuit. We compared two bloodpumps, the Jostra HL-20 heart-lung machine and the MEDOS DELTASTREAM DP1 Bloodpump, and two oxygenators, the Capiox Baby RX05 and the MEDOS HILITE 800LT, in terms of mean arterial pressure, energy equivalent pressure, surplus hemodynamic energy, total hemodynamic energy, and pressure drop over the oxygenators using a blood analog. The pumps and oxygenators were combined in unique circuits and tested in nonpulsatile and pulsatile modes, at two flow rates (500 and 800 mL/min), and three rotational speed differentials when using the MEDOS DELTASTREAM DP1 Bloodpump for 144 trials in total. The Jostra Roller pump produced some pulsatility in nonpulsatile mode and better pulsatility in pulsatile mode than the MEDOS DP1 Bloodpump at a rotational speed differential of 2500 rpm, but not at 3500 or 4500 rpm. The MEDOS DP1 Bloodpump produced almost no pulsatility in nonpulsatile mode. Pressure drops over the Capiox Baby RX05 were markedly higher, at 92.5 +/- 0.4 mm Hg with the MEDOS DP1 Bloodpump at 800 mL/min and 4500 rpm in pulsatile mode, than those of the MEDOS HILITE 800LT oxygenator, which was 67.0 +/- 0.1 mm Hg at the same settings. These results suggest that careful selection of each circuit component, based on the individual clinical case and component specifics, are necessary to achieve the best quality of pulsatility.

  2. Localization and synthesis of the hormone-binding regions of the human thyrotropin receptor

    SciTech Connect

    Atassi, M.Z.; Manshouri, T. ); Sakata, Shigeki )

    1991-05-01

    Two regions of human thyrotropin (thyroid-stimulating hormone, TSH) receptor (TSHR) were selected on the basis that they exhibit no sequence resemblance to luteinizing hormone/chorionic gonadotropin receptor. Five synthetic overlapping peptides (12-30, 24-44, 308-328, 324-344, and 339-364) were studied for their ability to bind {sup 125}I-labeled human TSH (hTSH), its isolated {alpha} and {beta} subunits, bovine TSH, ovine TSH, human luteinizing hormone, and human follicle-stimulating hormone. The human TSHR peptides 12-30 and 324-344 exhibited remarkable binding activity to human, bovine, and ovine TSH and to the {beta} chain of hTSH. Lower binding activity resided in the adjacent overlapping peptides, probably due to the contribution of the shared overlap to the binding. The specificity of TSH binding to these peptides was confirmed by their inability to bind human luteinizing hormone, human follicle-stimulating hormone, and the {alpha} chain of hTSH. Thyrotropins did not bind to bovine serum albumin or to peptide controls unrelated to the TSHR system. It is concluded that the binding of TSH to its receptor involves extensive contacts and that the TSHR peptides 12-30 and 324-344 contain specific binding regions for TSH that might be either independent sites or two faces (subsites) within a large binding site.

  3. Quantifying Pituitary-Adrenal Dynamics and Deconvolution of Concurrent Cortisol and Adrenocorticotropic Hormone Data by Compressed Sensing

    PubMed Central

    Faghih, Rose T.; Dahleh, Munther A.; Adler, Gail K.; Klerman, Elizabeth B.; Brown, Emery N.

    2015-01-01

    Pulsatile release of cortisol from the adrenal glands is governed by pulsatile release of adrenocorticotropic hormone (ACTH) from the anterior pituitary. In return, cortisol has a negative feedback effect on ACTH release. Simultaneous recording of ACTH and cortisol is not typical, and determining the number, timing, and amplitudes of pulsatile events from simultaneously recorded data is challenging because of several factors: (I) stimulator ACTH pulse activity, (II) kinematics of ACTH and cortisol, (III) the sampling interval, and (IV) the measurement error. We model ACTH and cortisol secretion simultaneously using a linear differential equations model with Gaussian errors and sparse pulsatile events as inputs to the model. We propose a novel framework for recovering pulses and parameters underlying the interactions between ACTH and cortisol. We recover the timing and amplitudes of pulses using compressed sensing, and employ generalized cross validation for determining the number of pulses. We analyze serum ACTH and cortisol levels sampled at 10-minute intervals over 24 hours from 10 healthy women. We recover physiologically plausible timing and amplitudes for these pulses and model the feedback effect of cortisol. We recover 15 to 18 pulses over 24 hours, which is highly consistent with the results of another cortisol data analysis approach. Modeling the interactions between ACTH and cortisol allows for accurate quantification of pulsatile events, and normal and pathological states. This could lay the basis for a more physiologically-based approach for administering cortisol therapeutically. The proposed approach can be adapted to deconvolve other pairs of hormones with similar interactions. PMID:25935025

  4. Quantifying Pituitary-Adrenal Dynamics and Deconvolution of Concurrent Cortisol and Adrenocorticotropic Hormone Data by Compressed Sensing.

    PubMed

    Faghih, Rose T; Dahleh, Munther A; Adler, Gail K; Klerman, Elizabeth B; Brown, Emery N

    2015-10-01

    Pulsatile release of cortisol from the adrenal glands is governed by pulsatile release of adrenocorticotropic hormone (ACTH) from the anterior pituitary. In return, cortisol has a negative feedback effect on ACTH release. Simultaneous recording of ACTH and cortisol is not typical, and determining the number, timing, and amplitudes of pulsatile events from simultaneously recorded data is challenging because of several factors: 1) stimulator ACTH pulse activity, 2) kinematics of ACTH and cortisol, 3) the sampling interval, and 4) the measurement error. We model ACTH and cortisol secretion simultaneously using a linear differential equations model with Gaussian errors and sparse pulsatile events as inputs to the model. We propose a novel framework for recovering pulses and parameters underlying the interactions between ACTH and cortisol. We recover the timing and amplitudes of pulses using compressed sensing and employ generalized cross validation for determining the number of pulses. We analyze serum ACTH and cortisol levels sampled at 10-min intervals over 24 h from ten healthy women. We recover physiologically plausible timing and amplitudes for these pulses and model the feedback effect of cortisol. We recover 15 to 18 pulses over 24 h, which is highly consistent with the results of another cortisol data analysis approach. Modeling the interactions between ACTH and cortisol allows for accurate quantification of pulsatile events, and normal and pathological states. This could lay the basis for a more physiologically-based approach for administering cortisol therapeutically. The proposed approach can be adapted to deconvolve other pairs of hormones with similar interactions.

  5. Measurement of pulsatile motion with millisecond resolution by MRI.

    PubMed

    Souchon, Rémi; Gennisson, Jean-Luc; Tanter, Mickael; Salomir, Rares; Chapelon, Jean-Yves; Rouvière, Olivier

    2012-06-01

    We investigated a technique based on phase-contrast cine MRI combined with deconvolution of the phase shift waveforms to measure rapidly varying pulsatile motion waveforms. The technique does not require steady-state displacement during motion encoding. Simulations and experiments were performed in porcine liver samples in view of a specific application, namely the observation of transient displacements induced by acoustic radiation force. Simulations illustrate the advantages and shortcomings of the methods. For experimental validation, the waveforms were acquired with an ultrafast ultrasound scanner (Supersonic Imagine Aixplorer), and the rates of decay of the waveforms (relaxation time) were compared. With bipolar motion-encoding gradient of 8.4 ms, the method was able to measure displacement waveforms with a temporal resolution of 1 ms over a time course of 40 ms. Reasonable agreement was found between the rate of decay of the waveforms measured in ultrasound (2.8 ms) and in MRI (2.7-3.3 ms).

  6. Experimental Fluid Mechanics of Pulsatile Artificial Blood Pumps

    NASA Astrophysics Data System (ADS)

    Deutsch, Steven; Tarbell, John M.; Manning, Keefe B.; Rosenberg, Gerson; Fontaine, Arnold A.

    2006-01-01

    The fluid mechanics of artificial blood pumps has been studied since the early 1970s in an attempt to understand and mitigate hemolysis and thrombus formation by the device. Pulsatile pumps are characterized by inlet jets that set up a rotational "washing" pattern during filling. Strong regurgitant jets through the closed artificial heart valves have Reynolds stresses on the order of 10,000 dynes/cm2 and are the most likely cause of red blood cell damage and platelet activation. Although the flow in the pump chamber appears benign, low wall shear stresses throughout the pump cycle can lead to thrombus formation at the wall of the smaller pumps (10 50 cc). The local fluid mechanics is critical. There is a need to rapidly measure or calculate the wall shear stress throughout the device so that the results may be easily incorporated into the design process.

  7. Ordered and random structures in pulsatile flow through constricted tubes

    NASA Astrophysics Data System (ADS)

    Lieber, B. B.

    The poststenotic flow field in a rigid tube was investigated under pulsatile conditions. The waveform employed in the present experiment was sinusoidal and three contoured constrictions with 50, 75, and 90% area reduction were investigated. The fluid dynamic similarity parameters were chosen to represent conditions found in large arteries of humans and of experimental animals, using a Reynolds number range of 200 to 1000 and a frequency parameter value of 5.3. The analysis techniques of autoregressive modeling, correlation methods, and phase-shift averaging were employed in order to extract the maximum information about flow behavior. Analysis focuses on identification and representation of coherent flow disturbances, and examination of the influence of core flow behavior on the cyclic wall shear stress.

  8. The Multiple Facets of Lutein: A Call for Further Investigation in the Perinatal Period

    PubMed Central

    Longini, Mariangela; Buonocore, Giuseppe

    2016-01-01

    Lutein may have important antioxidant actions in free-radical-mediated diseases, in addition to its well-known antioxidant and cytoprotective effects on macula and photoreceptors. The peculiar perinatal susceptibility to oxidative stress indicates that prophylactic use of antioxidants as lutein could help to prevent or at least to reduce oxidative stress related diseases in newborns. Since lutein is not synthesized by humans, the intake primarily depends on diet or supplementation. Newborns receive lutein exclusively from breast milk. Lutein supplementation in term newborns has been reported to reduce oxidative stress and increase antioxidant capacities in the first days of life. Innovative frontiers concerning lutein supplementation are orientated toward cardiometabolic health improvement and cognitive benefits. The safety of lutein as an antioxidant agent has been confirmed in experimental and clinical studies, but its routine use is not recommended in perinatal period. This review summarizes what is known about the role of lutein as an antioxidant and anti-inflammatory agent in animal model and humans. PMID:27668037

  9. Lutein and Age-Related Ocular Disorders in the Older Adult: A Review

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lutein, a carotenoid found in dark green, leafy vegetables, has been implicated as being protective against the acquired ocular diseases, such as cataracts and age-related macular degeneration. In the eye, lutein may act as an antioxidant and as a blue light filter to protect the underlying tissues ...

  10. A possible role for lutein and zeaxanthin in cognitive function in the elderly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological studies suggest that dietary lutein and zeaxanthin may be of benefit in maintaining cognitive health. Among the carotenoids, lutein and zeaxanthin, are the only two that cross the blood-retina barrier to form macular pigment (MP) in the eye. They also preferentially accumulate in hum...

  11. Ultrasound assisted extraction in quantifying lutein from chicken liver using high-performance liquid chromatography.

    PubMed

    Sun, Ting; Xu, Zhimin; Godber, J Samuel

    2006-01-02

    Four sample preparation methods, (1) solvent (SOL), (2) saponification and solvent (SP), (3) ultrasound assisted solvent (UA), and (4) saponification and ultrasound assisted solvent (SP-UA), were used for quantifying lutein in chicken liver samples by HPLC. The lutein concentrations obtained by using SOL, UA, SP, and SP-UA were significantly different with values from 10.4 microg/g (UA) to undetected (SOL). Efficiency of the four different methods for extracting lutein from high to low were the UA, SP, SP-UA, and SOL method. The measured value of lutein in the liver sample using the UA method was approximately two and three times higher than that obtained from the SP and SP-UA method, respectively. The methods with saponification significantly affected the stabilities of lutein in liver samples. The lutein concentration measured with the solvent only method was either much lower than any of the other extraction methods or undetectable. This indicated that little lutein in those samples was in a form that could be extracted directly by solvent. Compared with the saponification method, the ultrasound assisted solvent method could effectively extract lutein from sample matrix and thus avoid chemical degradation reactions, which would be especially important for complex biological tissue such as liver.

  12. Chlorella is an effective dietary source of lutein for human erythrocytes.

    PubMed

    Miyazawa, Taiki; Nakagawa, Kiyotaka; Kimura, Fumiko; Nakashima, Yuya; Maruyama, Isao; Higuchi, Ohki; Miyazawa, Teruo

    2013-01-01

    Chlorella contains a high amount of carotenoids, especially lutein, and has received attention as a possible dietary source for improving carotenoid levels in human blood. In the present study, we performed a 2-month single arm human study, and investigated the efficacy of Chlorella supplementation (9 g Chlorella/day; equivalent to 32 mg lutein/day) on lutein and other carotenoid concentrations in plasma as well as erythrocytes of 12 healthy subjects. Following Chlorella supplementation, lutein was the predominant carotenoid in erythrocytes, showing a 4-fold increase (from 14 to 54 pmol/mL packed cells). After the one month without Chlorella ingestion, erythrocyte lutein then decreased to a basal level (17 pmol/mL packed cells). Erythrocyte carotenoid (lutein, zeaxanthin, α-carotene, and β-carotene) levels were proportional to plasma carotenoid levels. The results suggest the transfer of Chlorella carotenoids, especially lutein, from plasma lipoprotein particles to the erythrocyte membrane. Chlorella intake would be effective for improving and maintaining lutein concentrations in human erythrocytes.

  13. Antioxidant properties of lutein contribute to the protection against lipopolysaccharide-induced uveitis in mice

    PubMed Central

    2011-01-01

    Background Lutein is an important eye-protective nutrient. This study investigates the protective effects and mechanisms of lutein on lipopolysaccharides (LPS)-induced uveitis in mice. Methods Lutein, suspended in drinking water at a final concentration of 12.5 and 25 mg/mL, was administered to mice at 0.1 mL/10 g body weight for five consecutive days. Control and model group received drinking water only. Uveitis was induced by injecting LPS (100 mg per mouse) into the footpad in the model and lutein groups on day 5 after the last drug administration. Eyes of the mice were collected 24 hours after the LPS injection for the detection of indicators using commercial kits and reverse transcription-polymerase chain reaction. Results LPS-induced uveitis was confirmed by significant pathological damage and increased the nitric oxide level in eye tissue of BALB/C mice 24 hours after the footpad injection. The elevated nitric oxide level was significantly reduced by oral administration of lutein (125 and 500 mg/kg/d for five days) before LPS injection. Moreover, lutein decreased the malondialdehyde content, increased the oxygen radical absorbance capacity level, glutathione, the vitamin C contents and total superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Lutein further increased expressions of copper-zinc SOD, manganese SOD and GPx mRNA. Conclusion The antioxidant properties of lutein contribute to the protection against LPS-induced uveitis, partially through the intervention of inflammation process. PMID:22040935

  14. Enhancing lutein productivity of an indigenous microalga Scenedesmus obliquus FSP-3 using light-related strategies.

    PubMed

    Ho, Shih-Hsin; Chan, Ming-Chang; Liu, Chen-Chun; Chen, Chun-Yen; Lee, Wen-Lung; Lee, Duu-Jong; Chang, Jo-Shu

    2014-01-01

    Lutein, one of the main photosynthetic pigments, is a promising natural product with both nutritional and pharmaceutical applications. In this study, light-related strategies were applied to enhance the cell growth and lutein production of a lutein-rich microalga Scenedesmus obliquus FSP-3. The results demonstrate that using white LED resulted in better lutein production efficiency when compared to the other three monochromatic LEDs (red, blue, and green). The lutein productivity of S. obliquus FSP-3 was further improved by adjusting the type of light source and light intensity. The optimal lutein productivity of 4.08 mg/L/d was obtained when using a TL5 fluorescent lamp at a light intensity of 300 μmol/m(2)/s, and this performance is better than that reported in most related studies. Moreover, the time-course profile of lutein accumulation in the microalga shows that the maximal lutein content and productivity were obtained at the onset of nitrogen depletion.

  15. Optimization of culture media for large-scale lutein production by heterotrophic Chlorella vulgaris.

    PubMed

    Jeon, Jin Young; Kwon, Ji-Sue; Kang, Soon Tae; Kim, Bo-Ra; Jung, Yuchul; Han, Jae Gap; Park, Joon Hyun; Hwang, Jae Kwan

    2014-01-01

    Lutein is a carotenoid with a purported role in protecting eyes from oxidative stress, particularly the high-energy photons of blue light. Statistical optimization was performed to growth media that supports a higher production of lutein by heterotrophically cultivated Chlorella vulgaris. The effect of media composition of C. vulgaris on lutein was examined using fractional factorial design (FFD) and central composite design (CCD). The results indicated that the presence of magnesium sulfate, EDTA-2Na, and trace metal solution significantly affected lutein production. The optimum concentrations for lutein production were found to be 0.34 g/L, 0.06 g/L, and 0.4 mL/L for MgSO4 ·7H2 O, EDTA-2Na, and trace metal solution, respectively. These values were validated using a 5-L jar fermenter. Lutein concentration was increased by almost 80% (139.64 ± 12.88 mg/L to 252.75 ± 12.92 mg/L) after 4 days. Moreover, the lutein concentration was not reduced as the cultivation was scaled up to 25,000 L (260.55 ± 3.23 mg/L) and 240,000 L (263.13 ± 2.72 mg/L). These observations suggest C. vulgaris as a potential lutein source.

  16. Neuroprotective Effect of Lutein on NMDA-Induced Retinal Ganglion Cell Injury in Rat Retina.

    PubMed

    Zhang, Chanjuan; Wang, Zhen; Zhao, Jiayi; Li, Qin; Huang, Cuiqin; Zhu, Lihong; Lu, Daxiang

    2016-05-01

    Lutein injection is a possible therapeutic approach for retinal diseases, but the molecular mechanism of its neuroprotective effect remains to be elucidated. The aim of this study was to investigate its protective effects in retinal ganglion cells (RGCs) against N-methyl-D-aspartate (NMDA)-induced retinal damage in vivo. Retinal damage was induced by intravitreal NMDA injection in rats. Each animal was given five daily intraperitoneal injections of Lutein or vehicle along with intravitreal NMDA injections. Electroretinograms were recorded. The number of viable RGCs was quantified using the retinal whole-mount method by immunofluorescence. Proteins were measured by Western blot assays. Lutein reduced the retinal damage and improved the response to light, as shown by an animal behavior assay (the black-and-white box method) in rats. Furthermore, Lutein treatment prevented the NMDA-induced reduction in phNR wave amplitude. Lutein increased RGC number after NMDA-induced retina damage. Most importantly, Bax, cytochrome c, p-p38 MAPK, and p-c-Jun were all upregulated in rats injected with NMDA, but these expression patterns were reversed by continuous Lutein uptake. Bcl-2, p-GSK-3β, and p-Akt in the Lutein-treated eyes were increased compared with the NMDA group. Lutein has neuroprotective effects against retinal damage, its protective effects may be partly mediated by its anti-excitability neurotoxicity, through MAPKs and PI3K/Akt signaling, suggesting a potential approach for suppressing retinal neural damage.

  17. Production, extraction and stabilization of lutein from microalga Chlorella sorokiniana MB-1.

    PubMed

    Chen, Chun-Yen; Jesisca; Hsieh, Chienyan; Lee, Duu-Jong; Chang, Chien-Hsiang; Chang, Jo-Shu

    2016-01-01

    The efficiencies of extraction and preservation of lutein from microalgae are critical for the success of its commercialization. In this study, lutein was produced by Chlorella sorokiniana MB-1 via semi-batch mixotrophic cultivation. The microalgal biomass with a lutein content of 5.21mg/g was pretreated by bead-beating and high pressure cell disruption methods, and the lutein content was harvested by a reduced pressure extraction method. The effect of pretreatment, pressure, solvent type, extraction time and temperature on lutein recovery was investigated. Using high pressure pretreatment followed by extraction with tetrahydrofuran (THF) as solvent resulted in high lutein recovery efficiencies of 87.0% (20min) and 99.5% (40min) at 850mbar and 25°C. In contrast, using ethanol as the solvent, 86.2% lutein recovery was achieved under 450mbar, 35°C and 40min extraction. The extracted lutein was stabilized in olive oil or sunflower oil with half-lives of 53.1 and 63.8days, respectively.

  18. New Insights into the Control of Pulsatile GnRH Release: The Role of Kiss1/Neurokinin B Neurons

    PubMed Central

    Navarro, Víctor M.

    2012-01-01

    Gonadotropin-releasing hormone (GnRH) is the ultimate output signal of an intricate network of neuroendocrine factors that, acting on the pituitary, trigger gonadotropin release. In turn, gonadotropins exert their trophic action on the gonads to stimulate the synthesis of sex steroids thus completing the gonadotropic axis through feedback regulatory mechanisms of GnRH release. These feedback loops are predominantly inhibitory in both sexes, leading to tonic pulsatile release of GnRH from puberty onward. However, in the female, rising levels of estradiol along the estrous cycle evoke an additional positive feedback that prompts a surge-like pattern of GnRH release prior to ovulation. Kisspeptins, secreted from hypothalamic Kiss1 neurons, are poised as major conduits to regulate this dual secretory pathway. Kiss1 neurons are diverse in origin, nature, and function, convening distinct neuronal populations in two main hypothalamic nuclei: the arcuate nucleus (ARC) and the anteroventral periventricular nucleus. Recent studies from our group and others point out Kiss1 neurons in the ARC as the plausible generator of GnRH pulses through a system of pulsatile kisspeptin release shaped by the coordinated action of neurokinin B (NKB) and dynorphin A (Dyn) that are co-expressed in Kiss1 neurons (so-called KNDy neurons). In this review, we aim to document the recent findings and working models directed toward the identification of the Kiss1-dependent mechanisms of GnRH release through a synoptic overview of the state-of-the-art in the field. PMID:22649420

  19. The Dorsomedial Suprachiasmatic Nucleus Times Circadian Expression of Kiss1 and the Luteinizing Hormone Surge

    PubMed Central

    Smarr, Benjamin L.; Morris, Emma

    2012-01-01

    Ovulation in mammals is gated by a master circadian clock in the suprachiasmatic nucleus (SCN). GnRH neurons represent the converging pathway through which the brain triggers ovulation, but precisely how the SCN times GnRH neurons is unknown. We tested the hypothesis that neurons expressing kisspeptin, a neuropeptide coded by the Kiss1 gene and necessary for the activation of GnRH cells during ovulation, represent a relay station for circadian information that times ovulation. We first show that the circadian increase of Kiss1 expression, as well as the activation of GnRH cells, relies on intact ipsilateral neural input from the SCN. Second, by desynchronizing the dorsomedial (dm) and ventrolateral (vl) subregions of the SCN, we show that a clock residing in the dmSCN acts independently of the light-dark cycle, and the vlSCN, to time Kiss1 expression in the anteroventral periventricular nucleus of the hypothalamus and that this rhythm is always in phase with the LH surge. In addition, we show that although the timing of the LH surge is governed by the dmSCN, its amplitude likely depends on the phase coherence between the vlSCN and dmSCN. Our results suggest that whereas dmSCN neuronal oscillators are sufficient to time the LH surge through input to kisspeptin cells in the anteroventral periventricular nucleus of the hypothalamus, the phase coherence among dmSCN, vlSCN, and extra-SCN oscillators is critical for shaping it. They also suggest that female reproductive disorders associated with nocturnal shift work could emerge from the desynchronization between subregional oscillators within the master circadian clock. PMID:22454148

  20. The dorsomedial suprachiasmatic nucleus times circadian expression of Kiss1 and the luteinizing hormone surge.

    PubMed

    Smarr, Benjamin L; Morris, Emma; de la Iglesia, Horacio O

    2012-06-01

    Ovulation in mammals is gated by a master circadian clock in the suprachiasmatic nucleus (SCN). GnRH neurons represent the converging pathway through which the brain triggers ovulation, but precisely how the SCN times GnRH neurons is unknown. We tested the hypothesis that neurons expressing kisspeptin, a neuropeptide coded by the Kiss1 gene and necessary for the activation of GnRH cells during ovulation, represent a relay station for circadian information that times ovulation. We first show that the circadian increase of Kiss1 expression, as well as the activation of GnRH cells, relies on intact ipsilateral neural input from the SCN. Second, by desynchronizing the dorsomedial (dm) and ventrolateral (vl) subregions of the SCN, we show that a clock residing in the dmSCN acts independently of the light-dark cycle, and the vlSCN, to time Kiss1 expression in the anteroventral periventricular nucleus of the hypothalamus and that this rhythm is always in phase with the LH surge. In addition, we show that although the timing of the LH surge is governed by the dmSCN, its amplitude likely depends on the phase coherence between the vlSCN and dmSCN. Our results suggest that whereas dmSCN neuronal oscillators are sufficient to time the LH surge through input to kisspeptin cells in the anteroventral periventricular nucleus of the hypothalamus, the phase coherence among dmSCN, vlSCN, and extra-SCN oscillators is critical for shaping it. They also suggest that female reproductive disorders associated with nocturnal shift work could emerge from the desynchronization between subregional oscillators within the master circadian clock.

  1. KNDy Neurons Modulate the Magnitude of the Steroid-Induced Luteinizing Hormone Surges in Ovariectomized Rats.

    PubMed

    Helena, Cleyde V; Toporikova, Natalia; Kalil, Bruna; Stathopoulos, Andrea M; Pogrebna, Veronika V; Carolino, Ruither O; Anselmo-Franci, Janete A; Bertram, Richard

    2015-11-01

    Kisspeptin is the most potent stimulator of LH release. There are two kisspeptin neuronal populations in the rodent brain: in the anteroventral periventricular nucleus (AVPV) and in the arcuate nucleus. The arcuate neurons coexpress kisspeptin, neurokinin B, and dynorphin and are called KNDy neurons. Because estradiol increases kisspeptin expression in the AVPV whereas it inhibits KNDy neurons, AVPV and KNDy neurons have been postulated to mediate the positive and negative feedback effects of estradiol on LH secretion, respectively. Yet the role of KNDy neurons during the positive feedback is not clear. In this study, ovariectomized rats were microinjected bilaterally into the arcuate nucleus with a saporin-conjugated neurokinin B receptor agonist for targeted ablation of approximately 70% of KNDy neurons. In oil-treated animals, ablation of KNDy neurons impaired the rise in LH after ovariectomy and kisspeptin content in both populations. In estradiol-treated animals, KNDy ablation did not influence the negative feedback of steroids during the morning. Surprisingly, KNDy ablation increased the steroid-induced LH surges, accompanied by an increase of kisspeptin content in the AVPV. This increase seems to be due to lack of dynorphin input from KNDy neurons to the AVPV as the following: 1) microinjections of a dynorphin antagonist into the AVPV significantly increased the LH surge in estradiol-treated rats, similar to KNDy ablation, and 2) intra-AVPV microinjections of dynorphin in KNDy-ablated rats restored LH surge levels. Our results suggest that KNDy neurons provide inhibition to AVPV kisspeptin neurons through dynorphin and thus regulate the amplitude of the steroid-induced LH surges.

  2. Effects of RFRP2 and RF9 on secretion of luteinizing hormone in prepubertal gilts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In most mammals, the RF-amide related peptide (RFRP) pre-pro-protein contains cleavage sites for 2 peptides (RFRP1 and RFRP3). Our laboratory did not observe RFRP3-induced suppression of LH secretion in gilts. However, the porcine sequence encodes an additional peptide (RFRP2) with an amidated C-ter...

  3. Pre-translational regulation of luteinizing hormone receptor in follicular somatic cells of cattle

    PubMed Central

    Marsters, P.; Kendall, N.R.; Campbell, B.K.

    2015-01-01

    Differential regulation of LHR in theca cells (TC) and granulosa cells (GC) is important for normal follicular development. Unlike TC, GC only acquire LH-responsiveness during the later stages of antral follicle development. This study tested the hypothesis that differential LH-responsiveness in these two cell types may be due, in part, to shifts in cellular patterns of alternatively spliced LHR mRNA transcripts which may not be obvious from analysis of total LHR gene expression. It also further explored the role of translation inhibition by an LHR binding protein (LHBP), normally associated with the production of endogenous cholesterol. LHR mRNA variation arises as a result of the alternative splicing of two variable deletion sites (VDS) designated 5′ VDS and 3′ VDS, and it was proposed that differences in cell sensitivity to LH may be due in part to variations in the pattern of the mRNA expression of the receptor variants. The outcomes of the present study support a dynamic multi-facetted regulation of LHR during pre-translation. Not only did the ratio between variants change during antral follicle growth and in vitro cell differentiation but also between TC and GC. Regulation could also be linked to LH concentration feedback mechanisms as the absence of LH caused cultured TC to markedly up-regulate amounts of LHR mRNA. In both TC and GC, LHR mRNA was greatly reduced after treatment to block mevalonate production in the de novo cholesterol pathway, adding further support for a regulatory mechanism linked to enriched cellular amounts of mevalonate kinase. PMID:26507944

  4. The pulsatility volume index: an indicator of cerebrovascular compliance based on fast magnetic resonance imaging of cardiac and respiratory pulsatility.

    PubMed

    Bianciardi, Marta; Toschi, Nicola; Polimeni, Jonathan R; Evans, Karleyton C; Bhat, Himanshu; Keil, Boris; Rosen, Bruce R; Boas, David A; Wald, Lawrence L

    2016-05-13

    The influence of cardiac activity on the viscoelastic properties of intracranial tissue is one of the mechanisms through which brain-heart interactions take place, and is implicated in cerebrovascular disease. Cerebrovascular disease risk is not fully explained by current risk factors, including arterial compliance. Cerebrovascular compliance is currently estimated indirectly through Doppler sonography and magnetic resonance imaging (MRI) measures of blood velocity changes. In order to meet the need for novel cerebrovascular disease risk factors, we aimed to design and validate an MRI indicator of cerebrovascular compliance based on direct endogenous measures of blood volume changes. We implemented a fast non-gated two-dimensional MRI pulse sequence based on echo-planar imaging (EPI) with ultra-short repetition time (approx. 30-50 ms), which stepped through slices every approximately 20 s. We constrained the solution of the Bloch equations for spins moving faster than a critical speed to produce an endogenous contrast primarily dependent on spin volume changes, and an approximately sixfold signal gain compared with Ernst angle acquisitions achieved by the use of a 90° flip angle. Using cardiac and respiratory peaks detected on physiological recordings, average cardiac and respiratory MRI pulse waveforms in several brain compartments were obtained at 7 Tesla, and used to derive a compliance indicator, the pulsatility volume index (pVI). The pVI, evaluated in larger cerebral arteries, displayed significant variation within and across vessels. Multi-echo EPI showed the presence of significant pulsatility effects in both S0 and [Formula: see text] signals, compatible with blood volume changes. Lastly, the pVI dynamically varied during breath-holding compared with normal breathing, as expected for a compliance indicator. In summary, we characterized and performed an initial validation of a novel MRI indicator of cerebrovascular compliance, which might prove useful

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

    PubMed

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

    2014-02-01

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

  6. Development of an antifertility vaccine for pets based on active immunization against luteinizing hormone-releasing hormone.

    PubMed

    Ladd, A; Tsong, Y Y; Walfield, A M; Thau, R

    1994-12-01

    Male dogs and cats were immunized against LHRH in order to evaluate the feasibility of an immunological approach to pet contraception. In the first study, dogs were immunized with 100, 500, or 2500 micrograms of LHRH conjugated to tetanus toxoid. A significant decline in serum testosterone (T) levels was observed in all immunized dogs, reaching castration levels in some animals by Week 4 and remaining suppressed in all the immunized dogs through the course of the study. Testicular histology suggested arrest of spermatogenesis (infertility). The effects of "immunological castration" were reversible (study 2): steroidogenesis suppressed by "immunological castration" was restored as antibody titers declined. Effective antibodies were rapidly reinduced in dogs by a single injection of LHRH1-TT. In contrast, the level of antibodies induced in male cats (study 3) was not sufficient for "immunological castration." The conclusion was that active immunization against LHRH could provide a cost-effective, nonsurgical, reversible means to control the fertility of companion animals.

  7. A conjugate of methotrexate and an analog of luteinizing hormone releasing hormone shows increased efficacy against prostate cancer

    PubMed Central

    Zhu, Shengsheng; Wang, Qinxia; Jiang, Juan; Luo, Yongwei; Sun, Zuyue

    2016-01-01

    LHRH receptor, is over-expressed in a variety of human tumors and, is a potential binding site for targeted metastatic prostate cancer therapy. The objectives of our study were to synthesize a bioconjugate of the LHRH analog [DLys6]-LHRH and the anti-tumor agent methotrexate and test the hypothesis that [DLys6]-LHRH-MTX targets and inhibits prostate cancer cell growth in vitro and in vivo. The results of in vitro studies, showed that both [DLys6]-LHRH-MTX and MTX displayed superior cytotoxicity against prostate cancer cells in a concentration-dependent manners, with IC50 concentrations for PC-3 cells of, 1.02 ± 0.18 μmol/L and 6.34 ± 1.01 μmol/L; for DU-145 cells, 1.53 ± 0.27 μmol/L and 8.03 ± 1.29 μmol/L; and for LNCaP cells, 1.93 ± 0.19 μmol/L and 9.68 ± 1.24 μmol/L, respectively. The IC50 values of [DLys6]-LHRH-MTX and MTX were 110.77 ± 15.31 μmol/L and 42.33 ± 7.25 μmol/L, respectively. Finally, [DLys6]-LHRH-MTX significantly improved the anti-tumor activity of MTX in nude mice bearing PC-3 tumor xenografts. The inhibition ratios of tumor volume and tumor weight in the [DLys6]-LHRH-MTX treated group were significantly higher than those in the MTX-treated group. Tumor volume doubling time was also significantly extended from 6.13 days in control animals to 9.67 days in mice treated with [DLys6]-LHRH-MTX. In conclusion, [DLys6]-LHRH -MTX may be useful in treating prostate cancer. PMID:27654169

  8. Sexual differentiation of oxytocin stress responsiveness: effect of neonatal androgenization, castration and a luteinizing hormone-releasing hormone antagonist.

    PubMed

    Carter, D A; Saridaki, E; Lightman, S L

    1988-04-01

    The plasma OT increment following stress in rats is sexually dimorphic, females exhibiting greater responses than males. We have investigated the role of neonatal androgen secretion in determining the sex-typical level of response. Castration of male pups either surgically or functionally (GnRH antagonist treatment) within either 2 h or 5 days of birth did not elevate the OT responses of adult males. In contrast, androgenization of female pups (testosterone, 1.25 mg/pup) within 5 days of birth markedly reduced the OT stress responses of adults to a level insignificantly different to males. The results show that neonatal androgens can exert organizational effects on OT regulatory mechanisms. Since neonatal castration was ineffective it would appear that a prenatal defeminization or masculinization event determines OT stress responsiveness in males.

  9. Physicochemical properties and storage stability of lutein microcapsules prepared with maltodextrins and sucrose by spray drying.

    PubMed

    Kuang, Pengqun; Zhang, Hongchao; Bajaj, Poonam R; Yuan, Qipeng; Tang, Juming; Chen, Shulin; Sablani, Shyam S

    2015-02-01

    The purpose of this study was to determine the physicochemical properties of lutein microcapsules. Nine types of lutein microcapsules were prepared in order to determine their encapsulation efficiency and yield. Results show that lutein microcapsules with maltodextrin M040 and sucrose at the weight ratio of 3:1 (designated as M040:1) had the highest encapsulation efficiency (90.1%) among the lutein microcapsules, as well as a higher encapsulation yield (90.4%). The onset glass transition temperatures (Tgi ) and the surface dents of the lutein microcapsules decreased as the dextrose equivalent value of maltodextrin and the weight ratio of sucrose increased. Enthalpy relaxation experiments were conducted for the lutein microcapsules M040:1 at (Tgi - 5) , (Tgi - 10), and (Tgi - 15) °C, and the obtained data were fitted to the Kohlrausch-Williams-Watts model. Results show that the mean relaxation time (τ) (316 h) of M040:1 lutein microcapsules aged at (Tgi - 15) °C was greater than the τ (161 h) at (Tgi - 10) °C and τ (60.5 h) at (Tgi - 5) °C. Effects of temperature and oxygen transmission rates for package film on the storage stability of M040:1 lutein microcapsules were also investigated. Findings show that rates of lutein degradation and color change increased by an order of magnitude as storage temperature (4 to 97 °C) and oxygen transmission rate of the package film (0.018 to 62.8 cc/m(2) day) increased. These results suggest that lutein is highly unstable and susceptible to thermal and oxidative degradations. However, microencapsulation with appropriate wall materials of higher relaxation time and high oxygen barrier packaging can increase the storage life.

  10. Arabidopsis carotenoid mutants demonstrate that lutein is not essential for photosynthesis in higher plants.

    PubMed Central

    Pogson, B; McDonald, K A; Truong, M; Britton, G; DellaPenna, D

    1996-01-01

    Lutein, a dihydroxy beta, epsilon-carotenoid, is the predominant carotenoid in photosynthetic plant tissue and plays a critical role in light-harvesting complex assembly and function. To further understand lutein synthesis and function, we isolated four lutein-deficient mutants of Arabidopsis that define two loci, lut1 and lut2 (for lutein deficient). These loci are required for lutein biosynthesis but not for the biosynthesis of beta, beta-carotenoids. The lut1 mutations are recessive, accumulate high levels of zeinoxanthin, which is the immediate precursor of lutein, and define lut1 as a disruption in epsilon ring hydroxylation. The lut2 mutations are semidominant, and their biochemical phenotype is consistent with a disruption of epsilon ring cyclization. The lut2 locus cosegregates with the recently isolated epsilon cyclase gene, thus, providing additional evidence that the lut2 alleles are mutations in the epsilon cyclase gene. It appears likely that the epsilon cyclase is a key step in regulating lutein levels and the ratio of lutein to beta,beta-carotenoids. Surprisingly, despite the absence of lutein, neither the lut1 nor lut2 mutation causes a visible deleterious phenotype or altered chlorophyll content, but both mutants have significantly higher levels of beta, beta-carotenoids. In particular, there is a stable increase in the xanthophyll cycle pigments (violaxanthin, antheraxanthin, and zeaxanthin) in both lut1 and lut2 mutants as well as an increase in zeinoxanthin in lut1 and beta-carotene in lut2. The accumulation of specific carotenoids is discussed as it pertains to the regulation of carotenoid biosynthesis and incorporation into the photosynthetic apparatus. Presumably, particular beta, beta-carotenoids are able to compensate functionally and structurally for lutein in the photosystems of Arabidopsis. PMID:8837513

  11. Exploratory metabolomic analyses reveal compounds correlated with lutein concentration in frontal cortex, hippocampus, and occipital cortex of human infant brain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with...

  12. College Students' Dietary Practices Affect Lutein/Zeaxanthin Intake: A Two-Generation, Ethnic and Gender Study

    ERIC Educational Resources Information Center

    Osaseri, Uyi E.; Kwok, Shiu Y.; Kwok, Wendy; Tam, Chick F.

    2008-01-01

    Lutein and zeaxanthin are important anti-oxidant nutrients obtained only from foods that are essential for good eye health. The purpose of this study was to assess food choices rich in lutein/zeaxanthin and compare the amount of lutein/zeaxanthin intake amongst college students and their live-in parents. Three-day dietary records from 95…

  13. Analysis of (all-E)-lutein and its (Z)-isomers during illumination in a model system.

    PubMed

    Li, Dajing; Xiao, Yadong; Zhang, Zhongyuan; Liu, Chunquan

    2014-11-01

    Light induced-isomerization of (all-E)-lutein in organic solvent and starch model systems was investigated. Lutein and its (Z)-isomers were separated by HPLC using a C30 column and gradient mobile phase based on methanol-methyl-tert-butyl ether-water in 24min. (All-E)-lutein and twelve (Z)-isomers of lutein, in addition a small amount of (all-E)-zeaxanthin and (9Z, 9'Z)-zeaxanthin were identified by HPLC-DAD-APCI-MS. Five di-(Z)-luteins were identified for the first time, namely, (9Z, 9'Z)-, (9Z, 13Z)/(9 Z, 13'Z)-, (13Z, 15Z)- and (9Z, 15Z)-lutein and (9Z, 9'Z)-zeaxanthin. A mixture of (9Z)-lutein and of (9'Z)-lutein was the main product of the iodine-catalyzed photo-isomerization. (9Z, 13Z)/(9Z, 13'Z)-lutein were the major di-(Z)-isomers of lutein formed. The susceptibility of lutein to degradation was much less under dark storage than under lighted storage in starch model system. Isomerization and degradation of lutein and its (Z)-isomers proceeded simultaneously in all the model systems.

  14. Pulsatile operation of the BiVACOR TAH - Motor design, control and hemodynamics.

    PubMed

    Kleinheyer, Matthias; Timms, Daniel L; Greatrex, Nicholas A; Masuzawa, Toru; Frazier, O Howard; Cohn, William E

    2014-01-01

    Although there is limited consensus about the strict requirement to deliver pulsatile perfusion to the human circulatory system, speed modulation of rotary blood pumps is an approach that may capture the benefits of both positive displacement and continuous flow blood pumps. In the current stage of development of the BiVACOR Total Artificial Heart emphasis is placed on providing pulsatile outflow from the pump. Multiple pulsatile speed profiles have been applied in preliminary in-vivo operation in order to assess the capability of the TAH to recreate a physiologic pulse. This paper provides an overview about recent research towards pulsatile BiVACOR operation with special emphasis on motor and control requirements and developments.

  15. Measurement of real pulsatile blood flow using X-ray PIV technique with CO2 microbubbles

    PubMed Central

    Park, Hanwook; Yeom, Eunseop; Seo, Seung-Jun; Lim, Jae-Hong; Lee, Sang-Joon

    2015-01-01

    Synchrotron X-ray imaging technique has been used to investigate biofluid flows in a non-destructive manner. This study aims to investigate the feasibility of the X-ray PIV technique with CO2 microbubbles as flow tracer for measurement of pulsatile blood flows under in vivo conditions. The traceability of CO2 microbubbles in a pulsatile flow was demonstrated through in vitro experiment. A rat extracorporeal bypass loop was used by connecting a tube between the abdominal aorta and jugular vein of a rat to obtain hemodynamic information of actual pulsatile blood flows without changing the hemorheological properties. The decrease in image contrast of the surrounding tissue was also investigated for in vivo applications of the proposed technique. This technique could be used to accurately measure whole velocity field information of real pulsatile blood flows and has strong potential for hemodynamic diagnosis of cardiovascular diseases. PMID:25744850

  16. Measurement of real pulsatile blood flow using X-ray PIV technique with CO2 microbubbles.

    PubMed

    Park, Hanwook; Yeom, Eunseop; Seo, Seung-Jun; Lim, Jae-Hong; Lee, Sang-Joon

    2015-03-06

    Synchrotron X-ray imaging technique has been used to investigate biofluid flows in a non-destructive manner. This study aims to investigate the feasibility of the X-ray PIV technique with CO2 microbubbles as flow tracer for measurement of pulsatile blood flows under in vivo conditions. The traceability of CO2 microbubbles in a pulsatile flow was demonstrated through in vitro experiment. A rat extracorporeal bypass loop was used by connecting a tube between the abdominal aorta and jugular vein of a rat to obtain hemodynamic information of actual pulsatile blood flows without changing the hemorheological properties. The decrease in image contrast of the surrounding tissue was also investigated for in vivo applications of the proposed technique. This technique could be used to accurately measure whole velocity field information of real pulsatile blood flows and has strong potential for hemodynamic diagnosis of cardiovascular diseases.

  17. Pulsatile flow into the aqueous veins: Manifestations in normal and glaucomatous eyes

    PubMed Central

    Johnstone, Murray; Martin, Elizabeth; Jamil, Annisa

    2015-01-01

    The aqueous outflow system is unique because nowhere else can the pattern of flow of an extravascular fluid be directly observed as it returns to the vascular system. Such observations reveal that aqueous flow both from Schlemm’s canal into the aqueous veins and from the aqueous veins into the episcleral veins is pulsatile. Pulsatile aqueous flow mechanisms are observable in vivo not only in normal and but also in glaucomatous eyes. A series of specific patterns accompany the pulsatile mixing of aqueous with blood in the episcleral veins. These directly observable patterns of pulsatile flow are synchronous with intraocular pressure (IOP) transients induced by the cardiac pulse, blinking and eye movement. Patterns of pulsatile flow are altered by events that increase IOP such as pressure on the side of the eye, tonography and water drinking. Pulsatile flow stops when IOP is reduced below its resting level, but begins again when IOP returns to the resting level. Pulsatile flow reduction probably results from the intrinsic reduction of pulse amplitude at a lower IOP, and may thus provide a passive mechanism to maintain short-term homeostasis. Thus modulation of the pulsatile flow phenomenon appears to maintain a homeostatic IOP setpoint. Visible pulsatile flow abnormalities develop in glaucoma patients. Medications that reduce IOP through improvement in outflow do so through pulsatile flow mechanisms. Laboratory studies have demonstrated that cyclic stresses in outflow tissues alter signaling pathways, cytoskeletal responses, extracellular matrix composition and cytokine secretion. How physiologic pulse transients orchestrate cellular responses and how cellular responses identified in the laboratory may in turn regulate pulsatile aqueous outflow is unknown. Linkage of laboratory and in vivo observations await an improved understanding of how cellular and extracellular structures within the outflow system are able to generate an aqueous pulse wave. The purpose of the

  18. High pulsatility flow stimulates smooth muscle cell hypertrophy and contractile protein expression

    PubMed Central

    Scott, Devon; Tan, Yan; Shandas, Robin; Stenmark, Kurt R.

    2013-01-01

    Proximal arterial stiffening is an important predictor of events in systemic and pulmonary hypertension, partly through its contribution to downstream vascular abnormalities. However, much remains undetermined regarding the mechanisms involved in the vascular changes induced by arterial stiffening. We therefore addressed the hypothesis that high pulsatility flow, caused by proximal arterial stiffening, induces downstream pulmonary artery endothelial cell (EC) dysfunction that in turn leads to phenotypic change of smooth muscle cells (SMCs). To test the hypothesis, we employed a model pulmonary circulation in which upstream compliance regulates the pulsatility of flow waves imposed onto a downstream vascular mimetic coculture composed of pulmonary ECs and SMCs. The effects of high pulsatility flow on SMCs were determined both in the presence and absence of ECs. In the presence of ECs, high pulsatility flow increased SMC size and expression of the contractile proteins, smooth muscle α-actin (SMA) and smooth muscle myosin heavy chain (SM-MHC), without affecting proliferation. In the absence of ECs, high pulsatility flow decreased SMC expression of SMA and SM-MHC, without affecting SMC size or proliferation. To identify the molecular signals involved in the EC-mediated SMC responses, mRNA and/or protein expression of vasoconstrictors [angiotensin-converting enzyme (ACE) and endothelin (ET)-1], vasodilator (eNOS), and growth factor (TGF-β1) in EC were examined. Results showed high pulsatility flow decreased eNOS and increased ACE, ET-1, and TGF-β1 expression. ACE inhibition with ramiprilat, ET-1 receptor inhibition with bosentan, and treatment with the vasodilator bradykinin prevented flow-induced, EC-dependent SMC changes. In conclusion, high pulsatility flow stimulated SMC hypertrophy and contractile protein expression by altering EC production of vasoactive mediators and cytokines, supporting the idea of a coupling between proximal vascular stiffening, flow

  19. Relationship between velocity profile and ultrasound echogenicity in pulsatile blood flows.

    PubMed

    Yeom, Eunseop; Lee, Sang Joon

    2015-01-01

    Pulsatile blood flows are easily found in the vessels of living organisms. Under pulsatile flow conditions, red blood cells (RBCs) are aggregated and dispersed repetitively. The phenomenon of RBC aggregation is an influential factor in hemorheological and hemodynamic properties. This study aims to investigate the relationship between velocity profile and RBC aggregation in pulsatile blood flows. A rat extracorporeal bypass model was adopted to generate a real pulsatile flow without changing the rheological properties. To check the stability of the experimental model, variations of the hemodynamic parameters were measured consecutively for 2 h. Ultrasound speckle images of the blood flow in the extracorporeal bypass loop were acquired using a 35-MHz ultrasound scanner. The velocity fields were measured by the speckle image velocimetry (SIV) method, in which the cross-correlation algorithm is applied to the speckle images. In addition, the RBC aggregation was estimated by analyzing the echogenicity distribution of the speckle images. The shape of the velocity profile was cyclically varied according to the cardiac cycle. This variation may be closely related to the variation of the echogenicity distribution in pulsatile flows. The simultaneous measurement of velocity and RBC aggregation would be useful for understanding the effects of the hemorheological features on the hemodynamic characteristics of pulsatile blood flows.

  20. A one-dimensional mathematical model for studying the pulsatile flow in microvascular networks.

    PubMed

    Pan, Qing; Wang, Ruofan; Reglin, Bettina; Cai, Guolong; Yan, Jing; Pries, Axel R; Ning, Gangmin

    2014-01-01

    Techniques that model microvascular hemodynamics have been developed for decades. While the physiological significance of pressure pulsatility is acknowledged, most of the microcirculatory models use steady flow approaches. To theoretically study the extent and transmission of pulsatility in microcirculation, dynamic models need to be developed. In this paper, we present a one-dimensional model to describe the dynamic behavior of microvascular blood flow. The model is applied to a microvascular network from a rat mesentery. Intravital microscopy was used to record the morphology and flow velocities in individual vessel segments, and boundaries are defined according to the experimental data. The system of governing equations constituting the model is solved numerically using the discontinuous Galerkin method. An implicit integration scheme is adopted to increase computing efficiency. The model allows the simulation of the dynamic properties of blood flow in microcirculatory networks, including the pressure pulsatility (quantified by a pulsatility index) and pulse wave velocity (PWV). From the main input arteriole to the main output venule, the pulsatility index decreases by 66.7%. PWV obtained along arterioles declines with decreasing diameters, with mean values of 77.16, 25.31, and 8.30 cm/s for diameters of 26.84, 17.46, and 13.33 μm, respectively. These results suggest that the 1D model developed is able to simulate the characteristics of pressure pulsatility and wave propagation in complex microvascular networks.

  1. Soy milk intake in relation to serum sex hormone levels in British men.

    PubMed

    Allen, N E; Appleby, P N; Davey, G K; Key, T J

    2001-01-01

    Soy beans contain high levels of the isoflavones genistein and daidzein and their glycosides and have been implicated in the prevention of prostate cancer, possibly via their effects on sex hormone metabolism. The aim of this study was to assess the relation between dietary soy intake and sex hormone levels in a cross-sectional analysis of 696 men with a wide range of soy intakes. Soy milk intake was measured using a validated semiquantitative food frequency questionnaire, and serum hormone concentrations were measured by immunoassay. Multiple regression was used to investigate the association between soy milk intake, an index of isoflavone intake, and hormone levels after adjustment for pertinent confounders. Soy milk intake was not associated with serum concentrations of testosterone, free testosterone, androstanediol glucuronide, sex hormone-binding globulin, or luteinizing hormone. These results suggest that soy milk intake, as a marker of isoflavone intake, is not associated with serum sex hormone concentrations among free-living Western men.

  2. Electrocardiogram-synchronized rotational speed change mode in rotary pumps could improve pulsatility.

    PubMed

    Ando, Masahiko; Nishimura, Takashi; Takewa, Yoshiaki; Yamazaki, Kenji; Kyo, Shunei; Ono, Minoru; Tsukiya, Tomonori; Mizuno, Toshihide; Taenaka, Yoshiyuki; Tatsumi, Eisuke

    2011-10-01

    Continuous-flow left ventricular assist devices (LVADs) have greatly improved the prognosis of patients with end-stage heart failure, even if continuous flow is different from physiological flow in that it has less pulsatility. A novel pump controller of continuous-flow LVADs has been developed, which can change its rotational speed (RS) in synchronization with the native cardiac cycle, and we speculated that pulsatile mode, which increases RS just in the systolic phase, can create more pulsatility than the current system with constant RS does. The purpose of the present study is to evaluate the effect of this pulsatile mode of continuous-flow LVADs on pulsatility in in vivo settings. Experiments were performed on eight adult goats (61.7 ± 7.5 kg). A centrifugal pump, EVAHEART (Sun Medical Technology Research Corporation, Nagano, Japan), was installed by the apex drainage and the descending aortic perfusion. A pacing lead for the detection of ventricular electrocardiogram was sutured on the anterior wall of the right ventricle. In the present study, we compared pulse pressure or other parameters in the following three conditions, including Circuit-Clamp (i.e., no pump support), Continuous mode (constant RS), and Pulsatile mode (increase RS in systole). Assist rate was calculated by dividing pump flow (PF) by the sum of PF and ascending aortic flow (AoF). In continuous and pulsatile modes, these assist rates were adjusted around 80-90%. The following three parameters were used to evaluate pulsatility, including pulse pressure, dp/dt of aortic pressure (AoP), and energy equivalent pulse pressure (EEP = (∫PF*AoP dt)/(∫PF dt), mm Hg). The percent difference between EEP and mean AoP is used as an indicator of pulsatility, and normally it is around 10% of mean AoP in physiological pulse. Both pulse pressure and mean dp/dt max were decreased in continuous mode compared with clamp condition, while those were regained by pulsatile mode nearly to clamp condition (pulse

  3. Association between Lutein and Zeaxanthin Status and the Risk of Cataract: A Meta-Analysis

    PubMed Central

    Liu, Xiao-Hong; Yu, Rong-Bin; Liu, Rong; Hao, Zhen-Xuan; Han, Cheng-Cheng; Zhu, Zhong-Hai; Ma, Le

    2014-01-01

    The purpose of this meta-analysis was to evaluate the relationship between blood lutein and zeaxanthin concentration and the risk of age-related cataract (ARC). MEDLINE, EMBASE, ISI and Cochrane Library were searched to identify relevant studies up to April 2013. Meta-analysis was conducted to obtain pooled relative risks (RRs) for the highest-versus-lowest categories of blood lutein and zeaxanthin concentrations. One cohort study and seven cross-sectional studies were included in the meta-analysis. There were significant inverse associations between nuclear cataract and blood lutein and zeaxanthin concentrations, with the pooled RRs ranging from 0.63 (95% confidence interval (CI): 0.49, 0.77) for zeaxanthin to 0.73 (95% CI: 0.59, 0.87) for