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Effect of Orexin Infusion into Third Ventricle on the GnRH and LH Secretions in the Prepubertal Rat  [PDF]
H. Khazali,M. Behzadfar
Journal of Applied Sciences , 2009,
Abstract: The goal of this study was to determine whether orexin affects gonadotropin releasing hormone (GnRH) and Luteinizing Hormone (LH) secretions in the prepubertal male and female rats. Forty prepubertal rats were randomly divided into 4 groups. Animals in group 1 and 2 were male and 3 and 4 were female. Animals in group 1 and 3 received infusions of 1 μg orexin and group 2 and 4 received infusions of 2 μg orexin into their third ventricle. Blood samples were collected from jugular veins, every 30 min from 4 h before the first infusion of orexin until 4 h after the last orexin infusion. Infusions of 1 and 2 μg orexin significantly (p<0.01) decreased the mean plasma concentrations and pulse amplitudes of GnRH and LH in prepubertal female animal. Also, infusions of 1 and 2 μg orexin significantly (p<0.05) decreased the mean plasma concentrations and pulse amplitudes of GnRH and LH in prepubertal male animal, but this decrease were lower in than female prepubertal rat. Infusions of 1 and 2 μg orexin did not change the mean plasma concentrations of FSH in the animal of all groups. Infusions of 1 and 2 μg, orexin significantly (p<0.01) decreased the glucose levels of the prepubertal female animals. The conclusion of this experiment indicated that orexin may negatively affect the GnRH and LH in the prepubertal rats with negative energy balance, but not in those with the positive energy balance.
A Two-Pathway Mathematical Model of the LH Response to GnRH that Predicts Self-Priming  [PDF]
J. J. Evans,T. M. Wilkinson,D. J. N. Wall
International Journal of Endocrinology , 2013, DOI: 10.1155/2013/410348
Abstract: An acute response of LH to a stimulatory pulse of GnRH is modelled as a result of a pathway (Pathway I) that consists of two compartments including a single (rate limiting) intermediate. In addition, a second pathway (Pathway II) was added, consisting of an intermediate transcription factor and subsequently a synthesised protein. Pathway II had a delayed effect on LH release due to the time taken to produce the intermediate protein. The model included synergism between these two pathways, which yielded an augmented response. The model accounts for a number of observations, including GnRH self-priming and the biphasic pattern of LH response. The same model was used to fit the data of the LH response when gonadotrophs responded to the addition of oxytocin in the response with a shoulder on the profile. Pathway I is able to be conceptualised as the basic Ca2+-mediated pathway. Pathway II contains features characteristic of the cAMP-mediated pathway. Thus, we have provided an explanation for details of the nature of the profile of LH secretion and additionally enabled incorporation of cAMP in an integrating model. The study investigated the possibility of two interacting pathways being at the basis of both the shoulder on the LH surges and self-priming, and the model illustrates that this appears to be highly likely. 1. Introduction The release of luteinising hormone (LH) from gonadotrophs is central to reproductive function. LH exhibits an episodic pattern, which is a result of gonadotropin-releasing hormone (GnRH) being transported from the hypothalamus to the pituitary in pulses. Following GnRH occupation of its cognate receptor on gonadotrophs, its stimulatory signal is transduced to the cell utilising associated intracellular pathways [1] and secretion of luteinising hormone (LH) occurs. In an oestrogenised environment, a process called GnRH self-priming occurs, whereby an initial pulse of GnRH primes the gonadotrophs in readiness for a subsequent pulse of GnRH. The complexity is such that it is impossible to establish the detailed components of a stimulatory pulse of GnRH with simple reductionist concepts. Some laboratories have begun to construct mathematical models of the processes that are involved. We document here a model that applies to the female gonadotrophs in the preovulatory, oestrogenised state. We produced a set of detailed data of the response in vitro, and for the model, we took note of the characteristics of the response: (i) a shoulder is present in the declining phase, (ii) enhancement occurs in a primed pulse, (iii) the enhancement
Prenatal testosterone treatment alters LH and testosterone responsiveness to GnRH agonist in male sheep
RECABARREN,SERGIO E; LOBOS,ALEJANDRO; FIGUEROA,YARA; PADMANABHAN,VASANTHA; FOSTER,DOUGLAS L; SIR-PETERMANN,TERESA;
Biological Research , 2007, DOI: 10.4067/S0716-97602007000400007
Abstract: although evidence is accumulating that prenatal testosterone (t) compromises reproductive function in the female, the effects of excess t in utero on the postnatal development of male reproductive function has not been studied. the aim of this study was to assess the influence of prenatal t excess on age-related changes in pituitary and gonadal responsiveness to gnrh in the male sheep. we used the gnrh agonist, leuprolide (10 μg/kg), as a pharmacologic challenge at 5, 10, 20 and 30 weeks of age. these time points correspond to early and late juvenile periods and the prepubertal and postpubertal periods of sexual development, respectively. lh and t were measured in blood samples collected before and after gnrh agonist administration. the area under the response curve (auc) of lh increased progressively in both controls and prenatal t-treated males from 5 to 20 weeks of age (p<0.01). the lh responses in prenatal t-treated males were lower at 20 and 30 weeks of age compared to controls (p<0.05). auc-t increased progressively in control males from 5 through 30 weeks of age and prenatal t-treated males from 5 to 20 weeks of age. the t response in prenatal t-treated males was higher at 20 weeks compared to controls of same age but similar to controls and prenatal t-treated males at 30 weeks of age (p <0.05). our findings suggest that prenatal t treatment advances the developmental trajectory of gonadal responsiveness to gnrh in male offspring
Prenatal testosterone treatment alters LH and testosterone responsiveness to GnRH agonist in male sheep
SERGIO E RECABARREN,ALEJANDRO LOBOS,YARA FIGUEROA,VASANTHA PADMANABHAN
Biological Research , 2007,
Abstract: Although evidence is accumulating that prenatal testosterone (T) compromises reproductive function in the female, the effects of excess T in utero on the postnatal development of male reproductive function has not been studied. The aim of this study was to assess the influence of prenatal T excess on age-related changes in pituitary and gonadal responsiveness to GnRH in the male sheep. We used the GnRH agonist, leuprolide (10 μg/kg), as a pharmacologic challenge at 5, 10, 20 and 30 weeks of age. These time points correspond to early and late juvenile periods and the prepubertal and postpubertal periods of sexual development, respectively. LH and T were measured in blood samples collected before and after GnRH agonist administration. The area under the response curve (AUC) of LH increased progressively in both controls and prenatal T-treated males from 5 to 20 weeks of age (P<0.01). The LH responses in prenatal T-treated males were lower at 20 and 30 weeks of age compared to controls (P<0.05). AUC-T increased progressively in control males from 5 through 30 weeks of age and prenatal T-treated males from 5 to 20 weeks of age. The T response in prenatal T-treated males was higher at 20 weeks compared to controls of same age but similar to controls and prenatal T-treated males at 30 weeks of age (P <0.05). Our findings suggest that prenatal T treatment advances the developmental trajectory of gonadal responsiveness to GnRH in male offspring
A mathematical model for LH release in response to continuous and pulsatile exposure of gonadotrophs to GnRH
Talitha M Washington, J Joseph Blum, Michael C Reed, P Michael Conn
Theoretical Biology and Medical Modelling , 2004, DOI: 10.1186/1742-4682-1-9
Abstract: Gonadotropin-releasing hormone (GnRH) is released by the hypothalamus in a pulsatile fashion and stimulates luteinizing hormone (LH) and follicle stimulating hormone (FSH) release by pituitary cells by a complex series of signaling processes. Although there is substantial information about various individual steps in the signaling system, there is less understanding of how these components interact to give rise to the overall behavior of the system. The frequency of pulses varies throughout the menstrual cycle increasing markedly just prior to ovulation. And, it has been observed in in vitro experiments on perifused pituitary cells that pulse frequency and concentration have marked (nonlinear) influences on the release of LH and FSH. The purpose of our work is to use mathematics and machine computation to understand the dynamics of this important and interesting physiological system.In a prior study, [1], a mathematical model was developed to investigate the rate of release of luteinizing hormone from pituitary gonadotrophs in response to short pulses of gonadotropin-releasing hormone. The model included binding of the hormone to its receptor, dimerization, interaction with a G-protein, production of inositoltrisphosphate (IP3), release of calcium from the endoplasmic reticulum (ER), entrance of calcium into the cytosol via voltage gated membrane channels, pumping of calcium out of the cytosol via membrane and ER pumps, and the release of luteinizing hormone (LH). Cytosolic calcium dynamics were simplified and it was assumed that there is only one pool of releasable LH. Despite these and other simplifications, the model results matched experimental curves and enabled us to understand the reasons for the qualitative features of the LH release curves in response to GnRH pulses of short durations and different concentrations both in the presence and absence of external calcium. We note that Heinze et al, [2], created a mathematical model for LH release that reproduces
A regulator of G Protein signaling, RGS3, inhibits gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) secretion
Jimmy D Neill, L Wayne Duck, Jeffrey C Sellers, Lois C Musgrove, John H Kehrl
BMC Cell Biology , 2001, DOI: 10.1186/1471-2121-2-21
Abstract: A truncated version of RGS3 (RGS3T = RGS3 314–519) inhibited gonadotropin releasing hormone-stimulated inositol trisphosphate production more potently than did RSG3 in gonadotropin releasing hormone receptor-bearing COS cells. An RSG3/glutathione-S-transferase fusion protein bound more 35S-Gqα than any other member of the G protein family tested. Adenoviral-mediated RGS3 gene transfer in pituitary gonadotropes inhibited gonadotropin releasing hormone-stimulated luteinizing hormone secretion in a dose-related fashion. Adeno-RGS3 also inhibited gonadotropin releasing hormone stimulated 3H-inositol phosphate accumulation, consistent with a molecular site of action at the Gqα protein.RGS3 inhibits gonadotropin releasing hormone-stimulated second messenger production (inositol trisphosphate) as well as luteinizing hormone secretion from rat pituitary gonadotropes apparently by binding and suppressing the transduction properties of Gqα protein function. A version of RGS3 that is amino-terminally truncated is even more potent than intact RGS3 at inhibiting gonadotropin releasing hormone-stimulated inositol trisphosphate production.A near-universal feature of cell signaling via seven transmembrane, G protein-coupled receptors is attenuation of a cellular response upon prolonged exposure to an extracellular stimulus [1]. This desensitization process is well-established for GnRH-stimulated LH secretion from pituitary gonadotropes [2,3], and occurs after about 6 h of continued exposure to GnRH in rats [3]; removal of GnRH permits recovery from the profound suppression of LH secretion, albeit rather slowly (2–4 days; 4). The molecular mechanisms involved in GnRH-induced desensitization are poorly understood, but they do not appear to be due to alterations in GnRH receptor expression [5,6] or to changes in LH concentrations in the pituitary gland [7,8].Earlier, we presented evidence that a regulator of G protein signaling, RGS3, might participate in the regulation of GnRH recept
Effects of recombinant LH supplementation to recombinant FSH during induced ovarian stimulation in the GnRH-agonist protocol: a matched case-control study
José G Franco, Ricardo LR Baruffi, Jo?o Oliveira, Ana L Mauri, Claudia G Petersen, Paula Contart, Valeria Felipe
Reproductive Biology and Endocrinology , 2009, DOI: 10.1186/1477-7827-7-58
Abstract: A total of 244 patients without ovulatory dysfunction, aged <40 years and at the first ICSI cycle were divided into two groups matched by age according to an ovarian stimulation scheme: Group I (n = 122): Down-regulation with GnRH-a + r-FSH and Group II (n = 122): Down-regulation with GnRH-a + r-FSH and r-LH (beginning simultaneously).The number of oocytes collected, the number of oocytes in metaphase II and fertilization rate were significantly lower in the Group I than in Group II (P = 0.036, P = 0.0014 and P = 0.017, respectively). In addition, the mean number of embryos produced per cycle and the mean number of frozen embryos per cycle were statistically lower (P = 0.0092 and P = 0.0008, respectively) in Group I than in Group II. Finally the cumulative implantation rate (fresh+thaw ed embryos) was significantly lower (P = 0.04) in Group I than in Group II. The other clinical and laboratory results analyzed did not show difference between groups.These data support r-LH supplementation in ovarian stimulation protocols with r-FSH and GnRH-a for assisted reproduction treatment.The pharmacology of ovarian stimulation has been strongly influenced by the two-cell, two-gonadotrophin theory [1] while, historically, follicular stimulation protocols have included both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in an attempt to mimic normal physiology [2]. During recent years, the effect of LH on follicular maturation and pregnancy outcome during the course of ovarian stimulation in relation to assisted reproduction has received increasing attention. This interest reflects the fact that modern stimulation protocols have resulted in substantially lower LH concentrations than those observed in the natural cycle and in previously used protocols. The introduction of gonadotrophin-releasing hormone agonists (GnRH-a) in the mid-1980s successfully circumvented the problems of a premature LH surge. There has also been a gradual shift from human gonadotrophin (H
大豆黄酮和雌二醇体外灌流公猪垂体组织对GnRH诱导下LH分泌的影响  [PDF]
王根林,陈杰,N.Parvizi
南京农业大学学报 , 1999, DOI: 10.7685/j.issn.1000-2030.1999.01.014
Abstract: 用不同浓度的大豆黄酮(Da,处理Ⅰ394nmol/L,处理Ⅱ7874nmol/L)和雌二醇(E2,处理Ⅲ100pmol/L,处理Ⅳ200pmol/L)体外灌流公猪垂体前叶组织,观察其对促黄体素(LH)分泌的影响。灌流24和48h后,Da和E2灌流组与对照组(处理Ⅴ)相比,垂体LH体外分泌水平都无明显差异。但在促性腺激素释放激素(GnRH)诱导下,各组LH分泌水平显著增加,诱导后20~30min出现分泌峰。GnRH诱导后1h,LH平均水平处理Ⅲ显著高于其他组(P<0.05或P<0.01);诱导后2h,处理Ⅱ和Ⅲ显著高于对照组(P<0.01),处理Ⅲ亦高于处理Ⅰ(P=0.05);诱导后3h,各组LH分泌无显著差异。结果表明,Da和E2对公猪垂体体外LH分泌无抑制作用,但对GnRH诱导的LH分泌有一定促进作用。
Indu??o da ovula??o em cabras, fora da esta??o reprodutiva, com LH e GnRH e com estro induzido por progestágenos
Leite, P.A.G.;Carvalho, G.R.;Rodrigues, M.T.;Ruas, J.R.M.;Amorim, E.A.M.;Maffili, V.V.;
Arquivo Brasileiro de Medicina Veterinária e Zootecnia , 2006, DOI: 10.1590/S0102-09352006000300012
Abstract: in order to achieve estrous synchronization, intravaginal sponges impregnated with 60mg of medroxyprogesterone acetate (mpa) were implanted in 45 goats for nine days. on day 7, 200iu of equine chorionic gonadotropin (ecg) and 37.5μg of cloprostenol were administered to each doe. the animals were randomly allocated in three treatments with 15 animals each. twenty four hours after intravaginal sponge removal, does were administered 1ml saline solution (control t1), 5mg lh (t2) and 2.5μg gnrh (t3) intramuscular injection. percentages of animals in estrus were 100.0; 73.3 and 66.6 (p<0.05) and average intervals from sponge removal to start of estrus were 34.8, 29.3 and 31.5 hours for t1, t2 and t3, respectively, being those differences not statistically significant. the average intervals from sponge removal to ovulation were 46.6, 52.1 and 41.6 hours for t1, t2 and t3, respectively, with the difference between t2 and t3 being statistically significant (p<0.01). ovulation time averages were 21.3, 26.8 and 22.3 hours after injections for t1, t2 and t3 , respectively.
《世界的虎》  [PDF]
马逸清
兽类学报 , 1988,
Abstract: ?虎是大型猛兽,近五十年来,虎的自然数量从10万只锐减为5千余只,已下降到十分危险的低度,因此,全球性的保护老虎引起各界人士的关注。
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