Induction of follicular growth and production of a normal hormonal milieu in spite of using a constant low dose of luteinizing hormone in women with hypogonadotrophic hypogonadism

This study was designed to examine ovarian performance, i.e.follicular growth, normal steroidogenesis and luteal phase function,following the administration of multiple increasing doses ofhuman follicle stimulating hormone (FSH) with a constant lowdose of luteinizing hormone (LH) in women with isolated hypogonadotrophichypogonadism. Human meno–pausal gonadotrophin (HMG) wasused in the first treatment cycle, starting with 150 IU of LHand 150 IU of FSH per day, for 7 days. The dose was increaseddaily with 75 IU of LH and 75 IU of FSH for another 7 days ifno response was detected by serial ultrasound measurements andserumoestradiol determinations. In the second treatment cycle,a constant dose of 75 IU of LH (using HMG) was administeredper day and up to 150 IU of FSH (using urofollitrophin) wassupplemented. If no response was detected after 7 days of treatment,the dose of FSH was increased. For the final stage of ovulationinduction, human chorionic gonadotrophin (HCG) was administeredin the presence of at least one follicle >17 mm in diameterbut with no more than three follicles >16mm in diameter.To verify the adequacy of the luteal phase, a pharmacokinetic/pharmacodynamicstudy of -HCG, oestradiol and progesterone was performed followingthe second treatment cycle only. Ovarian stimulation using aconstant dose of 75 IU of LH and increasing doses of FSH upto 225 IU, resulted in normal follicular growth and hormonalmilieu. Both women showed normal luteal phase oestradiol andprogesterone production and both women conceived following thesecond treatment cycle     

Gonadal axis hormones in male schizophrenic patients during treatment with haloperidol and after switch to risperidone

Rationale: The atypical neuroleptic risperidone, in addition to its dopamine receptor blocking activity, has a high affinity for serotonergic receptors. Since both dopaminergic and serotonergic neuronal activities participate in regulation of the pituitary – gonadal axis (PGA), it is expected that a switch from treatment with haloperidol to treatment with risperidone should influence plasma levels of PGA hormones. Objective: To study the effects of a drug with dopamine and serotonin receptor blocking activity on PGA hormones in patients who were on treatment with a dopamine receptor blocker. Methods: Plasma levels of testosterone, luteinizing harmone (LH) and follicle stimulating harmone (FSH), as well as prolactin and cortisol, were measured in 16 male schizophrenic patients during treatment with haloperidol (mean dose 23.3 mg daily, SD = 16.9) and 6 weeks later after switching to treatment with risperidone (mean dose 11.8 mg daily, SD = 2.9). Psychopathology was assessed by BPRS. Results: After switching to risperidone, total BPRS score and the scores in its subscales for positive, negative, and general symptoms were all significantly reduced in the order of 35–45%. Prolactin levels were significantly increased from 39.5 ± 22.3 to 58.9 ± 28.5 ng/ml (F = 4.61, P = 0.04), while cortisol, testosterone, LH, and FSH remained unchanged. No significant correlations between prolactin increases and reduction in BPRS or in its subscale scores were found. Conclusions: The results show that blocking of both dopamine and serotonin receptors does not influence the pituitary – gonadal axis but considerably increases prolactin release. Received: 29 June 1998/Final version: 23 October 1998     

An aminopeptidase inhibitor, bestatin, enhances progesterone and oestradiol secretion by porcine granulosa cells stimulated with follicle stimulating hormone in vitro

We examined the presence of cell surface aminopeptidase on culturedporcine granuiosa cells by employing the aminopeptidase assayusing alanine-p-nitroanilide and histochemical staining usingL-leucyl-β-naphthylamide. Porcine granuiosa cells obtainedfrom follicles 4–5 mm in diameter were cultured for 7days. The aminopeptidase assay showed that the porcine granuiosacell culture had aminopeptidase activity and that this activitywas inhibited in a dose-dependent manner by bestatin which bindsto cell surfaces and inhibits cell surface aminopeptidases.Histochemical staining also indicated that cultured granuiosacells had aminopeptidase activity. Porcine granuiosa cells werecultured in the presence or absence of porcine follicle stimulatinghormone (FSH, 3.125 nmol/1) and/or bestatin (0.4, 4.0 and 40.0µ/ml) for 7 days, and the production of progesterone andoestradiol was measured. In the presence of porcine FSH, theproduction of progesterone and oestradiol by granuiosa cellswas increased significantly by 5- and 2-fold respectively. Theseincreases were enhanced further by bestatin (40.0 (µg/ml).In the absence of porcine FSH, progesterone production was enhancedby bestatin (40.0 µg/ml), whereas no significant effectof bestatin on oestradiol secretion was observed. These findingsindicate that the inhibition of membrane-bound amino-peptidase(s)on the cell surfaces affects the steroidogenesis of granuiosacells, and that these aminopeptidase(s) are important regulatorsof granuiosa cell differentiation.     

年龄、基础卵泡刺激素值对控制性促超排卵结局的预测价值

目的 探讨年龄、基础卵泡刺激素（FSH）值对控制性促超排卵（COH）结局的预测价值。方法 对2003年1月至2004年11月在同济医院生殖中心行体外受精（IVF）／单个精子卵母细胞内注射（ICSI）与胚胎移植（ET）助孕术的1252个周期结局进行回顾性分析。结果 随年龄、基础FSH值的上升，获卵数和可移植胚胎数逐渐减少，周期取消率逐渐升高。但在基础FSH值≤18mU／ml时，只有年龄与临床妊娠显著相关，而基础FSH值与临床妊娠无显著相关性。结论 年龄、基础FSH值的上升与COH结果负性相关，而年龄则是妊娠的独立预测因子。     

激素替代治疗子宫内膜异位症根治术后42例疗效观察

目的:探讨应用激素替代治疗改善子宫内膜异位症根治术后围绝经期症状的疗效和安全性。方法:2002年1月~2004年12月因重度子宫内膜异位症行根治术出现围绝经期症状的患者42例,随机分成2组。观察组22例口服倍美力0.3 mg,1次/d,对照组20例口服利维爱1.25 mg,1次/d。治疗前后检测血清FSH(卵泡刺激素)和E2(雌二醇)水平,记录治疗期间盆腔痛、性交痛等子宫内膜异位症相关症状,Kupperm an(K评分)1次/月。结果:两组治疗后围绝经期症状均明显改善,血清E2水平上升,治疗前后比较差异有显著性意义(P<0.01),无内膜异位症复发表现。治疗后的E2水平观察组高于对照组,两组比较差异有显著性意义(P<0.01),但均在安全范围内。结论:小剂量倍美力和利维爱用于重度子宫内膜异位症根治术后患者,能有效地控制围绝经期症状,安全,无复发。     

心理应激对大鼠睾丸细胞FSH及LH表达的影响研究

目的: 探讨心理应激对大鼠睾丸细胞卵泡剌激素(FollicStimulatingHormone, FSH) 和黄体生成素(LuteinizingHormone, LH)表达的影响。方法: 采用心理应激大鼠模型, 以免疫组化与微机图象分析相结合技术, 观察大鼠心理应激后睾丸间质细胞和其它间质组织FSH、LH的表达程度, 微机检测睾丸间质FSH、LH阳性产物的相对光密度及细胞体积密度(VV) 和FSH、LH阳性的睾丸间质细胞数密度(NV) 的变化。结果: (1)A组(闪光间期长短不均加电剌激组)、B组(闪光间期恒定加电剌激组)和C组(单纯闪光间期长短不均组)三组比较,在睾丸间质细胞、血管壁外膜和其它间质组织的FSH、LH阳性表达强度、FSH、LH阳性产物相对光密度及FSH、LH阳性的睾丸间质细胞VV和NV等参数组间, 均显示出明显的差异, 即A组FSH、LH免疫染色切片比较, LH阳性表达明显强于FSH。结论: 心理应激对大鼠睾丸细胞FSH、LH的表达均有显著抑制作用。     

女性不同性激素水平下脑源性神经营养因子的变化

目的:观察女性不同性激素水平下脑源性神经营养因子(brain-derived neurotrophic factor,BD-NF)的变化.方法:临床纳入62例围绝经期及绝经后妇女,根据STRAW分期以及绝经年限长短进行分组,同时纳入16例健康育龄妇女作为对照组.分别采集所有入组者的血液标本,检测血清雌二醇(E2)、睾酮(T)、卵泡刺激素(FSH)以及BDNF的水平.结果:围绝经期组以及绝经后的妇女,血清BD-NF水平明显低于健康育龄妇女,BDNF水平与E2水平有明显相关性(r=0.302,P=0.016).结论:血清BDNF水平与脑源性雌激素水平有着密切的联系.     

Follistatin suppresses FSHbeta but increases LHbeta expression in the goldfish - evidence for an activin-mediated autocrine/paracrine system in fish pituitary

Our previous study demonstrated that recombinant goldfish activin B stimulated goldfish FSHbeta but inhibited LHbeta expression. Similar to activin B, activin A also exhibited the inverse effects on the expression of the two gonadotropins. The novel dual effects of activins on FSH and LH in the goldfish raise an interesting question as to where the activin comes from in vivo. In the present study, we first demonstrated the expression of activin, its receptors and binding protein follistatin in the goldfish pituitary, leading to a suggestion that an autocrine/paracrine regulatory system involving activin is operative in fish pituitary. To investigate the functionality of the pituitary-derived activin system in the regulation of gonadotropin biosynthesis, we further examined the effects of follistatin, an activin-binding protein, on goldfish FSHbeta and LHbeta expression. Follistatin not only reversed the effects of exogenous activin on FSHbeta and LHbeta expression but also had inverse effects on the basal expression of the genes; and its effects were opposite to those of activin. This suggests that the endogenous activin plays roles in controlling the expression of both FSHbeta and LHbeta genes. It is conceivable that any factors that influence the intrapituitary activin system in vivo will likely affect the biosynthesis of the two gonadotropins in the goldfish.