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低氧对若干生殖内分泌激素水平的影响及其调节机制
史小军
导师杜继曾
1997
学位授予单位中国科学院西北高原生物研究所
学位授予地点中国科学院西北高原生物研究所
学位专业动物学
摘要低氧作为一种特殊的应激源,诱发机体产生广泛的应答。关于低氧对呼吸、循环、血液、免疫等系统影响的研究已有不少的文献报道,有关低氧对生殖内分泌系统影响的研究报道尚不多见。近年来,人们对低氧生理的研究开始注重神经与内分泌系统的低氧作用。因而全面系统地研究低氧对生殖内分泌激素水平的影响及其调控机制,无疑是对低氧生物学研究领域的新贡献。本文以雄性实验动物大鼠和高原土著动物高原鼠兔为研究对象,在由下丘脑、垂体构成的生殖内分泌调节中枢,生殖腺和外周靶器官等三个层次上,较全面系统地研究模拟海拔 5km、7km 高度,急性、亚急性、慢性低氧暴露对生殖内分泌不同层次激素水平的作用形式、规律与特点;探讨神经肽 CRF、AVP 与单胺类神经递质 NE 参与低氧应激大鼠生殖内分泌激素水平的调节机制。结果如下:一.急性低氧暴露(2h、24h),7km 组下丘脑 GnRH 含量明显降低,5km 组无明显影响;低氧使垂体 LH 水平明显增高,以 7km 增高最为明显;2.亚急性低氧暴露,下丘脑 GnRH 和垂体 LH 水平与对照组之间均无显著差异,但血浆 T 仍旧维持一较高水平,7km 组睾丸指数明显增加;3.慢性低氧暴露,使 7km 组下丘脑 GnRH 水平明显降低,5km 组与对照组下丘脑 GnRH 含量比较,已无明显差异。7km 和 5km 低氧组垂体 LH 与对照组间无明显差异。慢怀低氧使血浆 T 水平明显降低。5km、7km 低氧组睾丸指数增高尤以 7km 组增高明显,睾丸曲细精管间隙增大,5km 组精原细胞质内线粒体聚集,7km 组管膜类肌层中出现空泡,精原细胞及支持细胞间质中出现空泡,各级生精细胞排裂絮乱等器质性改变。二.下丘脑神经肽 CRF、AVP 及神经递 NE 对低氧应激大鼠生殖内分泌的影响1.高剂量 icv CRF 使低氧应激大鼠下丘脑 GnRH 含量增加,CRF 抗血清对低氧应激大鼠下丘脑 GnRH 水平无明显作用;中枢 CRF 尚能明显降低低氧应激大鼠血浆 T 水平。2.icv avp 使低氧应激大鼠下丘脑 GnRH 含量明显增加,icv CRF 抗血清和 AVP 拮抗剂,降低低氧应激大鼠下丘脑 GnRH 含量。icv AVP 不明显影响低氧应激大鼠垂体 LH 水平,icv DPArg 效果亦然。3.icv NE 使低氧应激大鼠下丘脑 GnRH 含量明显增高,利血平具有降低、α-受体阻断剂有增加低氧应激大鼠下丘脑 GnRH 水平的趋势。 β--受体阻断剂心得安能明显降低低氧应激大鼠下丘脑 GnRH 含量。去肾上腺后,低氧应激大鼠下丘脑 GnRH 水平明显增加。利血平和α-受体阻断剂对低氧应激大鼠垂体 LH 水平无明显影响。此外,icv NE 明显使血浆 T 水平增高,利血平化后,低氧应激大鼠血浆 T 含量极明显降低,α-受体阻断剂使血浆 T 明显降低。三.低氧对高原鼠兔生殖内分泌激素的影响1 急性 24h 低氧,7km 组高原鼠兔下丘脑 GnRH 水平明显降低,血浆 E_2 水平增高。2.亚急性低氧对高原鼠兔下丘脑 GnRH 水平无明显影响,血浆 E_2 水平仍明显高于对照,7km 组睾丸指数明显降低。3.慢性低氧暴露使 7km 组下丘脑 GnRH 水平增高;血浆 E_2 水平仍高于对照。结论:1.急性低氧应激刺激下丘脑 GnRH 和血浆 T 水平分泌,抑制垂体 LH 分泌。2.亚急性低氧,下丘脑 GnRH 及垂体 LH 均维持一种积极调整机对代偿平衡的状态。3.低血浆 T 水平、下丘脑 GnRH 含量降低及睾丸组织民生器质性的改变证明,7km 慢性低氧暴露,影响生殖内分泌功能。4.神经递质 NE 参与低氧应激对生殖内分泌激素的影响。NE 对低氧应激大鼠下丘脑 GnRH 分泌有抑制作用,为β-肾上腺能受体所介导;α-肾上腺能受体参与 NE 促血浆 T 分泌作用。5.神经肽 CRF 抑制低氧应激大鼠下丘脑 GnRH 的分泌,中枢 icv CRF 具抑制低氧应激大鼠血浆 T 水平的作用。6.AVP 对低氧应激大鼠生殖内分泌激素的影响,发生在下丘脑水平且与 CRF 协同对 GnRH 分泌产生抑制作用。7.雄性高原鼠兔下丘脑 GnRH 和性腺激素 E_2 对低氧刺激有明显应答。血浆 E_2 水平增高,是高原鼠兔区别于大鼠对低氧反应的特征。
其他摘要Hypoxia, as an unspecific stress factor, has wide effects on the whole body which result in a series of responses. A lot of research articles concerning the effects of hypoxia on respiratory and circulating systems have been published in last several decades. However, no systematic work appears to have been carried out, particularly about the effects of hypoxia on HPG-axis and the modulating mechanism in altitude circumstance. This paper mainly testifies the influences of acute and chronic hypoxia exposures on the HPG-axis of male rats and male plateau pikas by means of simulating different altitudes in different periods of time of hypoxia exposure, further to reveal the mechanisms by which neuropeptides CRF, AVP and neurotransmitter NE involved in the regulating to reproductive endocrine functions of the rats exposed to acute hypoxia.The experiment results showed that: 1. For male rats: 1.1. The levels of hypothalamic GnRH decreased after acute hypoxia exposure for 2h and 24h at the altitude of 7 km; the levels of pituitary LH and plasma T at altitudes of both 5 km and 7 km increased. 1.2. After hypoxic exposure for 7d, the levels of both hypothalamic GnRH and pituitary LH of rats exposed to hypoxia of 5km and 7km had no obvious changes comparing to controls, but the plasma T still kept at a high level, meanwhile the ratio of testis weight to body mass appeared to increase especially in 7km altitude group. 1.3. The chronically hypoxic exposure reduced the levels of hypothalamic GnRH and had no obvious effect on the content of pituitary LH in both of 7km and 5km hypoxia groups, the levels of plasma T decreased significantly with the ratio of testis weight to body mass being still lower than control. The noticeably histomorphologic changes observed in the testicular is that the gaps among seminiferous tubule enlarged obviously with spermotogenic cells of different stages arranging in disorder and vesicles appeared in the membrane of seminiferous tubule even in the cytoplasm. 2. The influence of neuropeptides CRF, AVP and neurotransmitter NE on male rats exposed to acute hypoxia: 2.1. After icv a high dose of CRF, the levels of hypothalamic GnRH increased with a depression of plasma T. 2.2. It was observed that extraneous AVP exerted inhibitory effects upon secretion of hypothalamic GnRH without remarkable effects on the levels of pituitary LH. Treatment of AVP antagonist (DPArg) exhibited less effective on hypothalamic GnRH as well as the level of pituitary LH. However, it appeared to reduce the contents of hypothalamic GnRH via coadministration of CRF antiserum and DPArg together. 2.3. The levels of hypothalamic GnRH elevated significantly by icv NE. It was shown that administration of reserpine (ip) and prazosin (α-antagonist, icv) exerted decreasing and increasing tendency on the levels of hypothalamic GnRH respectively, on the contrary, icv propranolol reduced hypothalamic GnRH contents of male rats exposed to acute hypoxia. 3. The influence of hypoxia on the levels of reproductive hormones of male plateau pikas: 3.1. The levels of hypothalamic GnRH of pikas, after exposed to 7 km hypoxia for 24h, appeared to be decreased with increased levels of plasma E_2. 3.2. The levels of hypothalamic GnRH increased and there were no obviously histomorphologic changes in the testicular of pikas during serious chronic hypoxia exposure.Conclusions:1. Acute hypoxia stimulated the secretion of hypothalamic GnRH and the plasma T, but suppressed the release of the pituitary LH.2. Hypoxic exposure for 7 days had no remarkable effect on both hypothalamic GnRH and pituitary LH, but plasma T still kept in a higher level.3. In chronic hypoxia exposure experiment, the endocrine function of HPG-axis is inhibited obviously at the altitude of 7km.4. Norepinephrine is involved in the effect of hypoxia on the hormone levels of HPG-axis.The inhibition of NE on hypothalamic GnRH is mediated by β-adrenergic receptor and α-adrenergic receptor played a role in facilitating T secretion.5. Neuropeptide CRF and AVP suppress the secretion of hypothalamic GnRH of male rats exposed to acute hypoxia and centrally icv CRF induces a inhibition on the secretion of plasma T.6. The reproductive hormones of hypothalamic GnRH and gonadal T in male pikas are affected by simulated hypoxia. The higher level of serum E_2 appeared to be a characteristic response to hypoxic exposure.
页数85
语种中文
文献类型学位论文
条目标识符http://210.75.249.4/handle/363003/3364
专题中国科学院西北高原生物研究所
推荐引用方式
GB/T 7714
史小军. 低氧对若干生殖内分泌激素水平的影响及其调节机制[D]. 中国科学院西北高原生物研究所. 中国科学院西北高原生物研究所,1997.
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