育龄女性应用促性腺激素释放激素类似物与促性腺激素释放激素激发试验的对比研究

目的探讨皮下注射促性腺激素释放激素类似物(GnRHa)激发试验与传统的静脉推注促性腺激素释放激素(GnRH)激发试验对育龄女性下丘脑-垂体-性腺轴功能的评价是否具有一致性。方法以2010年5月至7月在新疆自治区人民医院进行健康体检的20名20~30岁女性为研究对象,采用配对设计对20名女性先后进行GnRH和GnRHa激发试验,两试验均在用药前及用药后120 min之内的7个时间点采血留取标本,应用化学发光法测定黄体生成素(LH)和卵泡刺激素(FSH)。对检测结果进行比较和分析。结果在GnRH和GnRHa激发试验中,7个时间点之间LH的差异均有统计学意义(U=154.0,P<0.01),FSH的差异也均有统计学意义(U=5.598,P<0.01)。两激发试验得到的相应的7个时点的LH进行比较后可以发现,仅在90 min(P=0.037)及120 min(P=0.013)两个时间点差异有统计学意义;FSH仅在120 min时差异有统计学意义(P=0.017)。结论在育龄女性,GnRHa对LH的影响在0~60 min与GnRH一致,对FSH的影响在0~90 min与GnRH一致。因此,在一定程度上可以替代GnRH用于激发试验,并且可以简化为60 min一次采血激发试验来对受试者下丘脑-垂体-性腺轴功能进行评价。     

松花粉对D-半乳糖亚急性衰老模型大鼠下丘脑-垂体-睾丸轴的调节作用

目的 探讨松花粉的抗下丘脑-垂体-睾丸衰老作用。方法 D-半乳糖连续腹腔注射制作亚急性衰老雄性大鼠模型，分别采用放射免疫和酶联免疫法检测血清中黄体生成激素（LH）、卵泡刺激素（FSH）、胰岛素样生长因子1（IGF-1）、睾酮（T）含量以及下丘脑促性腺激素释放激素（GnRH）浓度的变化。结果 D-半乳糖所致亚急性衰老大鼠模型组LH、FSH、GnRH均明显上升，IGF-1、睾酮含量明显下降。与正常对照组比较差异显著（P〈0．01）；而经松花粉给药后LH、FSH、GnRH三者均有显著下降，IGF-1、车酮含量明显提高。结论 松花粉具有改善衰老雄性大鼠卞丘脑-垂体-睾丸轴功能紊乱的作用。     

雌二醇对动情间期切除卵巢母羊黄体生成激素脉冲分泌的抑制作用

12只动情间期母羊切除卵巢后,根据随机皮下植入或不植入E_2而分为二组。通过颈静脉插管每5～10分钟采血一次,连续8～9小时,分离血浆作LH放免测定。实验组的平均LH基础分泌水平和LH脉冲幅高比对照组显著减低,LH脉冲频率无明显改变。LH的平均基础分泌水平和脉冲幅高显著相关。本研究表明,植入E_2抑制垂体LH的分泌,其作用可能主要是抑制LH对GnRH的反应,因此,作用部位是在垂体水平。LH基础分泌水平的下降,亦可能是E_2的抑制作用所致。     

男性Grave''s病患者垂体促性腺激素和性激素分泌的变化

目的　探讨高甲状腺激素对男性垂体促性腺激素和性激素分泌的影响。方法　对15例初诊男性Grave’s病患者分别在治疗前和治疗后 8～ 13个月进行促性腺激素释放激素(GnRH)兴奋试验 ,观察垂体促性腺激素黄体生成素 (LH)、卵泡刺激素 (FSH )和泌乳素 (PRL)和性激素 [睾酮 (T)和雌二醇 (E2 ) ]水平及对GnRH刺激的反应 ,计算曲线下面积 ,同时测定性激素结合球蛋白 (SHBG)水平 ,并以 9名正常人作为对照组 ,进行比较。结果　Grave’s病患者LH和FSH水平显著高于对照组 (P <0 .0 5或P <0 .0 1) ,对GnRH刺激反应也增强 ;T和SHBG升高 ,PRL和E2无明显变化 ,E2 /T则明显低于对照组水平 (P <0 .0 5 )。甲状腺激素和T与SHBG呈显著正相关 (P<0 .0 1)。经过治疗 ,甲状腺功能恢复正常后上述异常指标均恢复至正常水平。结论　高甲状腺激素时垂体促性腺激素细胞分泌和储备功能增强 ,而这种改变是可逆的。     

经皮下注射GnRH:吸收动力学和促性腺激素反应

本文目的旨在评价对GnRH反应的下丘脑性闭经妇女,经皮下注射GnRH后,脉冲式释放GnRH的可行性。将结果与经静脉给药相对比。 方法:选择5名年龄23～33岁的对克罗米芬无反应的下丘脑性闭经妇女作为研究对象。与健康妇女的早期卵泡期指数进行比较,受试者的血浆FSH值正常,血浆LH值正常或偏低。一次静脉注射25μgGnRH,5名妇女的血浆LH和FSH均增高。在注射GnRH前及注射后2,5,10,15,20,30,45,     

贵州省地方性克汀病垂体—性腺系统功能对LHRH兴奋试验的反应

在已经加碘得到控制的碘缺乏性疾病病区,观察了地方性克汀病垂体--性腺系统对促黄体激素释放因子(LHRH)试验的反应。结果:男性克汀病病人组血清黄体生成激素(LH)和卵泡刺激素(FSH)基础值显著高于对照组,但其血清睾酮(T)值则显著低于对照组。静脉注射 LHRH100μg15分钟后,克汀病病人组血清 FSH 反应高于正常人组,LH 反应与正常对照组相似。两组血清 T 值于试验后无显著变化。静脉注射接着静脉滴注 LHRH,克汀病病人组 FSH 反应高于正常人,其 LH 最大增值和反应倍数均低于对照组,正常人组 LH、FSH 呈双相反应,克汀病病人组则无此反应。血清 T,正常人组试验后2-3小时显著升高,克汀病病人组无则显著变化。结果表明克汀病病人不仅有原发性 Leydig 和 Sertoli 细胞功能低下,而且还有垂体促性腺激素储备和再合成功能的减低。     

睾酮对GnRH拮抗剂抑制的大鼠垂体和血清FSH的刺激作用

GnRH拮抗剂直接阻断GnRH受体,从而抑制垂体和睾丸的功能。最近动物实验研究表明,补充睾酮能延迟GnRH拮抗剂抑制精子生成的作用,防止垂体和血清FSH水平大幅度下降。为明确GnRH拮抗剂处理后再补充睾酮是否能使FSH水平回升,作者采用体重350～400g成。年雄性Sprague-Daw-ley大鼠,为为50％丙二醇赋形剂(1、2组)和RS-68439GnRH拮抗剂(3、4、5组)进行对     

垂体促性腺激素水平变化及对老年病的影响

促性腺激素卵泡刺激素(FSH)和黄体生成素(LH)是垂体细胞合成、分泌的多功能激素,除影响生殖系统外,还具有多重生理功能,参与老化相关疾病的发生与发展.随年龄增长,中枢神经垂体功能减退,FSH、LH合成与分泌随之发生变化,这种变化与动脉硬化性心血管疾病、代谢异常等老化相关疾病关系密切,调节FSH、LH可能成为相关疾病防...     

老年女性脑梗死者下丘脑-垂体-卵巢轴功能变化研究

目的探讨绝经后老年脑梗死患者下丘脑垂体卵巢轴功能变化的特点及意义。方法采用放免法动态测定97例老年女性脑梗死患者血清促卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)及睾酮(T)的水平。分析其与病程、病情、梗死部位及梗死范围的关系。结果(1)老年女性脑梗死患者急性期血清FSH、LH、E2值下降,T值升高,与恢复期及对照组比较,差异有统计学意义(P<0.01);恢复期血清FSH、LH、E2、T同对照组相比,无显著差异(P>0.05)。(2)急性期中、重型组血清FSH、E2、T的水平明显高于轻型组,差异有统计学意义(P<0.05);2组间血清LH无明显差异(P>0.05)。(3)急性期皮质组、皮质下组、混合组比较,梗死范围≥2cm×2cm×2cm组与梗死范围<2cm×2cm×2cm组比较,血清FSH、LH、E2、T值均无显著差异(P>0.05)。结论老年女性脑梗死患者急性期存在下丘脑垂体卵巢轴功能紊乱,随着疾病的好转趋于正常。且这种紊乱不受梗死部位及梗死范围的影响,与病情程度密切相关。     

促性腺激素诱导卵巢高激动期间血浆抑制素水平——卵泡功能的一种新指标

长期认为性腺分泌一种调节卵泡刺激素(FS-H)激动的非类固醇因子——抑制素,抑制垂体分泌FSH。目前已从牛与猪的卵泡液中提纯出来,克隆化并弄清楚其顺序。牛抑制素是分子量58KD的糖蛋白,含43KD与15KD两个亚单位,制成含20     

Inhibin concentrations in ovarian and jugular venous plasma and the relationship of inhibin with follicle-stimulating hormone and luteinizing hormone during the ovine estrous cycle

A heterologous RIA for ovine inhibin was developed which was sufficiently sensitive and specific to describe the peripheral concentrations of immunoreactive inhibin (iINH) during the estrous cycle of the ewe and to examine the effects of cautery of ovarian follicles on concentrations of iINH in ovarian and jugular venous plasma. Parallel logit-log dose-response lines were observed among ovine follicular fluid, ewe plasma, and pure native ovine (31 kDa) and bovine (31 kDa) inhibin. iINH could not be detected in ovariectomized ewe plasma, and there was no apparent cross-reactivity with a variety of structurally related and unrelated hormones and peptides, except a monomeric form of the alpha-subunit of INH, iINH in follicular fluid was 10(4)-fold higher than that in ovarian venous plasma, which was 3-fold higher than that in peripheral plasma. Cautery of the follicles resulted in a 35% reduction in iINH and an 81% reduction in estrogen concentrations in the ovarian vein within 10 min. During the estrous cycle, iINH and FSH were inversely related in samples taken over 30 h in the luteal phase (r = -0.69; P less than 0.001) and in the pre- and postovulatory phases (r = -0.45; P less than 0.001). iINH and LH were not related in the luteal phase, but were weakly positively correlated in the follicular phase (r = 0.31; P less than 0.01). iINH and estrogen concentrations in the follicular phase were also weakly correlated (r = 0.30; P less than 0.001). Furthermore, iINH concentrations rose in the follicular phase and decreased within 3-6 h of the preovulatory surges of LH and FSH, reaching a nadir around the time of the second rise in FSH 24-48 h later. It is concluded that 1) large antral follicles are a major source of peripheral iINH during the ovine estrous cycle; 2) iINH levels increase in the follicular phase with the growth of the dominant follicle and may be inhibited by the preovulatory surge of gonadotropin; 3) the fall in inhibin after the LH surge may be responsible for the second rise in FSH; and 4) the inverse relationship between FSH and iINH is consistent with the hypothesis that inhibin is involved in the feedback regulation of FSH.     

Increase in ovulation rate after active immunization of sheep with inhibin partially purified from bovine follicular fluid

Four Romney ewes were actively immunized with a partially purified preparation of inhibin derived from bovine follicular fluid and their ovulation rates in four successive oestrous cycles were compared with those of four ewes receiving adjuvant alone. The ovulation rates of the ewes immunized with the inhibin preparation were significantly higher than those of the control ewes (2.06 +/- 0.16 (S.E.M.) vs 1.31 +/- 0.06 ovulations/ewe, n = 4). Plasma concentrations of FSH and LH, measured in blood samples taken three times a week for 11 weeks, during which time each ewe was immunized three times, were not significantly different between the two treatment groups. These results suggest that active immunization with inhibin-enriched follicular fluid may be a potential means of increasing fecundity in sheep.     

Inhibin immunoneutralization by antibodies raised against synthetic peptide sequences of inhibin alpha subunit: effects on gonadotrophin concentrations and ovulation rate in sheep

Two experiments were conducted to explore the effectiveness of synthetic peptide-based vaccines for active and passive autoimmunization of sheep against inhibin. In the first experiment, adult Romney ewes (n = 20) were actively immunized against a synthetically produced peptide that corresponded to the N-terminus of the alpha-subunit of bovine inhibin (bI alpha(1-29)-Tyr30). This peptide was conjugated to tuberculin purified protein derivative (PPD) to increase its antigenic properties. Control groups comprised non-immunized (n = 10) and PPD-immunized (n = 10) ewes. Primary immunization (400 micrograms conjugate/ewe) was followed by two booster immunizations (200 micrograms conjugate/ewe), given 5 and 8 weeks later. Following synchronization of oestrus using progestagen sponges, ovulation rates were assessed by laparoscopy. Weekly blood samples were taken throughout the experiment. All inhibin-immunized ewes produced antibodies which bound 125I-labelled bovine inhibin (Mr 32,000), and ovulation rate in inhibin-immunized ewes (2.15 +/- 0.22; mean +/- S.E.M.) was significantly (P less than 0.01) greater than in both non-immunized (0.90 +/- 0.23) and PPD-immunized (1.20 +/- 0.13) control groups. Immunization against the peptide, but not against PPD alone, resulted in a modest rise in plasma FSH, with mean levels after the second boost being significantly (P less than 0.025) higher (22%) than those before immunization. Moreover, when blood samples were taken (2-h intervals) from randomly selected groups of control (n = 7) and inhibin-immunized (n = 7) ewes for an 84-h period following withdrawal of progestagen sponges, the mean plasma concentration of FSH during the 48 h immediately before the preovulatory LH surge was 37% greater (P less than 0.025) in immunized than in control animals. However, more frequent blood sampling (every 15 min for 12 h) during follicular and mid-luteal phases of the oestrous cycle revealed no significant differences between treatment groups in mean plasma concentrations of FSH. In addition, neither mean concentrations of LH nor the frequency and amplitude of LH episodes differed between immunized and control ewes. However, the mean response of LH to a 2 micrograms bolus of gonadotrophin-releasing hormone, given during the luteal phase, was significantly (P less than 0.05) less in immunized than in control ewes. These findings indicate that active immunization of Romney ewes against a synthetic fragment of inhibin can promote a controlled increase in ovulation rate, but this response cannot be unequivocally related to an increase in plasma levels of FSH.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of inhibin like factors on gonadotrophin release by the mouse pituitary in vitro

The release of gonadotrophins by the mouse whole pituitary in vitro was investigated. Whole tissue from 34 day old male mice was highly responsive to synthetic LRH in short incubations at 37 degrees C. About 15% of FSH and 17% of LH were secreted during a 3 h pulse with 3 ng of LRH. Pre-exposure of the mouse pituitary to fractions containing inhibin activity, inhibited the FSH release induced by LRH. Inhibin from bovine and human seminal plasma and porcine follicular fluid preferentially inhibited FSH secretion, while LH secretion was also reduced by inhibin like factors from bovine follicular fluid and testicular extract. The inhibition of FSH and/or LH release was measured by specific radioreceptor assays and could not be due to destruction of either gonadotrophin or LRH. Purified bovine seminal plasma inhibin was effective at very low concentrations in vitro. The whole incubation system is simple and an estimation of inhibition of bioactive (binding activity) FSH release can be obtained within 24 h.     

Changes in the secretion of LH pulses, FSH and prolactin during the preovulatory phase of the oestrous cycle of the ewe and the influence of treatment with bovine follicular fluid during the luteal phase

It has previously been shown that treatment of ewes with bovine follicular fluid (bFF) throughout the luteal phase of the oestrous cycle lowers plasma levels of FSH but increases the frequency and amplitude of the pulses of LH. Under these conditions, ovarian follicles grow to a maximum diameter of 2.7 mm and have a reduced capacity to release oestradiol. We have examined the nature of the gonadotrophin signals controlling follicular development in the normally cycling ewe and have investigated the effects of previous exposure to bFF on these signals and the follicular responses to them. Control ewes (n = 7) were injected i.v. with 9 ml bovine serum and treated ewes were injected with 9 ml bFF, twice daily from days 1 to 10 of the luteal phase (day 0 = oestrus). The ewes were injected with prostaglandin analogue on day 11 of the cycle to induce luteolysis and the gonadotrophin patterns were studied in blood sampled from these animals every 10 min for up to 72 h during the subsequent follicular phase. Following luteolysis (and the end of bFF treatment), LH pulse frequency increased rapidly in both groups and reached 1 pulse/h within 6 h. Thereafter, pulse frequency increased marginally and reached 1 pulse/50 min by the onset of the LH surge. This pattern was not affected by previous treatment with bFF. In the control ewes, the amplitude of the LH pulses did not change significantly following luteolysis or at any time during the follicular phase, while the levels of FSH declined slowly until the onset of the surge. In the treated ewes, on the other hand, there was an immediate increase in both LH pulse amplitude and the concentration of FSH immediately after the end of bFF treatment at luteolysis, and they remained above control levels for 24 and 16 h respectively. Plasma prolactin levels did not appear to change around the time of luteolysis but showed a marked and significant diurnal rhythm (nadir around noon and peak around midnight) in both groups. The concentrations of prolactin were significantly (P less than 0.001) lower and the preovulatory peak was delayed and reduced in the bFF-treated ewes relative to controls. The onset of oestrus was also significantly (P less than 0.01) delayed by bFF treatment, but the ovulation rates did not differ between the groups. Furthermore, comparisons within or between groups revealed no significant relationships between any of the variables of plasma LH secretion during the follicular phase and the subsequent ovulation rate.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of bovine follicular fluid on the secretion of LH and FSH in inhibin-immunized seasonally anoestrous ewes

It has been shown previously that treatment of seasonally anoestrous ewes with steroid-free bovine follicular fluid (FF), a crude inhibin-containing preparation, leads to a decrease in plasma FSH level which is accompanied by a marked increase in pulsatile LH secretion. Since FF contains several factors (e.g. activin, follistatin, unidentified components) other than inhibin, which might act to modify gonadotrophin secretion, it was of interest to establish whether these concurrent effects of FF on FSH and LH secretion persisted in ewes which had been actively immunized against a synthetic peptide replica of the alpha subunit of bovine inhibin. In June 1989 (anoestrous period) groups of inhibin-immune and control ewes (n = 5 per group) received 6-hourly s.c. injections of either bovine serum (2 ml) or one of two doses of FF (0.5 ml or 2 ml) for 3 days. Blood was withdrawn at 6-h intervals for 6 days beginning 24 h before the first injection. On the final day of treatment, additional blood samples were withdrawn at 15-min intervals for 8 h to monitor pulsatile LH secretion. Ewes were then challenged with exogenous gonadotrophin-releasing hormone (GnRH; 2 micrograms i.v. bolus) to assess pituitary responsiveness. In control ewes, FF promoted a dose-dependent suppression of basal (maximum suppression 65%; P less than 0.01) and post-GnRH (maximum suppression 72%; P less than 0.01) levels of FSH in plasma. This was accompanied by an increase (P less than 0.01) in LH pulse frequency from 1.40 +/- 0.24 (S.E.M.) to 3.20 +/- 0.37 pulses/8 h. In contrast, FF did not affect secretion of either FSH or LH in inhibin-immunized ewes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of crude and highly purified bovine inhibin (Mr 32,000 form) on gonadotrophin production by ovine pituitary cells in vitro: inhibin enhances gonadotrophin-releasing hormone-induced release of LH

Primary cultures of ovine pituitary cells (from adult ewes) were used to investigate the actions of steroid-free bovine follicular fluid (bFF) and highly-purified Mr 32,000 bovine inhibin on basal and gonadotrophin-releasing hormone (GnRH)-induced release of FSH and LH. Residual cellular contents of each hormone were also determined allowing total gonadotrophin content/well to be calculated. As in rats, both crude and highly purified inhibin preparations promoted a dose (P less than 0.001)- and time (P less than 0.001)-dependent suppression of basal and GnRH-induced release of FSH as well as an inhibition of FSH synthesis, reflected by a fall in total FSH content/well. However, while neither inhibin preparation affected basal release of LH or total LH content/well, GnRH-induced LH release was significantly (P less than 0.001) increased by the presence of either bFF (+75%) or highly-purified inhibin (+64%) in a dose- and time-dependent manner. This unexpected action of bFF on GnRH-induced LH release was abolished in the presence of 5 microliters specific anti-inhibin serum, confirming that the response was indeed mediated by inhibin. Furthermore, neither oestradiol-17 beta (1 pmol/1-10 nmol/l) nor monomeric alpha-subunit of bovine inhibin (2.5-40 ng/ml) significantly affected basal or GnRH-induced release of LH. These in-vitro findings for the ewe lend support to a number of recent in-vivo observations and indicate that, in addition to its well-documented suppressive effect on the synthesis and secretion of FSH, inhibin may actually facilitate LH release in this species, in marked contrast to its action in the rat.     

The antagonistic effect of exogenous LH pulses on FSH-stimulated preovulatory follicle growth in ewes chronically treated with a gonadotrophin-releasing hormone agonist

The hypogonadotrophism model induced by the chronic administration of gonadotrophin-releasing hormone (GnRH) agonist was used to investigate the effects of different concentrations of FSH with or without LH pulses on the stimulation of follicular development in the ewe. Continuous administration of an agonist (buserelin) by osmotic minipump to thirty-six Welsh Mountain ewes from the early luteal phase for 5 weeks resulted in a sustained suppression of the plasma concentration of FSH and inhibited the pulsatile release of LH. The inhibition of gonadotrophin secretion was due to the desensitization and/or down-regulation of pituitary gonadotroph function, since the agonist-treated animals showed no response to a challenge of 1 microgram GnRH. During week 6 of agonist treatment, ewes were infused with either 4-hourly pulses of ovine LH (9 micrograms/pulse), low concentrations of ovine FSH (3 micrograms/h) or high concentrations of FSH (9 micrograms/h) alone or with 4-hourly pulses of LH. After 5 days of gonadotrophin infusion, there was no difference between the mean number of follicles per ewe from the animals treated with LH alone, low concentrations of FSH with or without LH pulses or the high concentration of FSH alone compared with the mean number of follicles from control ewes on day 8 of the luteal phase. Infusion of the high concentration of FSH alone stimulated the development of an increased number of large oestrogenic follicles (follicles greater than 2.5 mm in diameter and secreting greater than 3.7 nmol oestradiol/h in vitro) compared with control ewes. The addition of high-amplitude LH pulses to the infusion of the high concentration of FSH prevented follicles developing beyond 2.5 mm in diameter, but doubled the number of small follicles (less than or equal to 2.5 mm) present in the ovaries. These results show that normal follicular development can be induced by physiological concentrations of FSH alone in the absence of pulsatile LH release. The addition of high-amplitude LH pulses antagonized this stimulatory effect of FSH on follicle growth in the ewe.     

Effects of porcine follicular fluid on gonadotropin concentrations in rhesus monkeys

The administration of steroid-free charcoal-treated porcine follicular fluid to long term castrated female rhesus monkeys lowered basal serum concentrations of FSH and had almost no effect on serum LH. Treatment with porcine follicular fluid before the administration of exogenous LRH inhibited the release of FSH, but also affected the release of LH. This inhibition was especially striking on the suppression of the peak of release of both FSH or LH at 20 min. These findings suggest that an inhibin-like material present in follicular fluid could play an important role in the secretion of FSH and LH in rhesus monkeys.     

Effects of ovarian inhibin on pulsatile release of gonadotrophins and secretion of LHRH in ovariectomized rats: evidence against a central action of inhibin

Intraperitoneal administration of bovine follicular fluid (bFF) decreased plasma concentrations of FSH in ovariectomized rats after 2-3 h, while plasma LH and prolactin were unaffected. In untreated ovariectomized animals the concentrations of these hormones were found to show pulsatile variations. Concomitant occurrence of peak values of LH and FSH was found in about 40% of the pulses. No pulses of FSH were observed after i.p. treatment with bFF or partly purified preparations of inhibin from bFF, but the pulsatile release of LH and prolactin remained similar. Infusion of bFF into the lateral ventricle of the brain did not alter the concentrations of FSH, whereas administration of bFF into the pituitary gland diminished the plasma concentrations of FSH. Anaesthesia (urethane plus xylazine) did not prevent the occurrence of the pulses of FSH and LH, but it reduced the pulse amplitude and clearance. During this anaesthesia, the concentrations of LHRH in the hypophysial stalk plasma decreased by 30% after administration of bFF, but did not alter after treatment with partly purified preparations of inhibin. It is concluded that the inhibin-like activity in bFF suppresses pulsatile FSH secretion in ovariectomized rats by an action on the pituitary gland, but has no effect on the pulsatile release of LH and prolactin.