Follicular oestrogen synthesis: the ‘two-cell, two-gonadotrophin’ model revisited

The original ‘two-cell mechanism’ explained the endocrine regulation of follicular oestrogen synthesis and implied paracrine signalling in the follicle wall. It is now known that the CYP17 gene encoding 17-hydroxylase/ C_17–20-lyase activity crucial to androgen synthesis, is expressed exclusively in thecal cells. 17-Hydroxylase/C_17–20-lyase activity is regulated by LH and subject to local modulation by a factor(s) emanating in FSH-stimulated granulosa cells. The FSH receptor gene is expressed exclusively in granulosa cells, where FSH acts directly to induce cytoproliferation and differentiation via cyclic AMP/protein kinase-A mediated post-receptor signalling. Granulosa cells also express androgen receptors, and theca-derived androgen has the potential to modulate locally differentiative responses to FSH. When follicles are recruited to preovulatory development by FSH, their granulosa cells develop LH receptors functionally coupled to aromatase activity and inhibin production. Thereby they simultaneously undertake LH-responsive aromatization and inhibin synthesis. Inhibin has the potential to potently enhance LH-stimulated thecal androgen synthesis. Granulosa-derived inhibin may therefore participate in a paracrine mechanism that locally amplifies androgen synthesis, and hence oestrogen formation, in the preovulatory follicle(s).     

Ovarian steroids modify the behavioral and neurochemical responses of the central benzodiazepine receptor

The effect of ovarian steroids on the benzodiazepine receptor was assessed in the elevated plus-maze and, after restraint stress, in benzodiazepine receptor binding assays. Vehicle-treated proestrous rats displayed anxiolytic behavior, relative to diestrous or estrous rats. Anxiolytic behavior was observed after 1 or 2 mg/kg diazepam in diestrus and estrus. However, whereas 4 mg/kg increased open arm exploration in diestrus, a decrease in the same measure was found at estrus. At proestrus, a decrease in anxiolytic behavior was observed after 2 and 4 mg/kg. In ovariectomized vehicletreated rats, restraint stress increased NaCl-induced potentiation of³H-flunitrazepam binding in cortical and cerebellar, but not in hippocampal membranes. Estradiol benzoate (2 µg) prevented the potentiation of flunitrazepam binding by NaCl in nonstressed and stressed animals, whereas progesterone (0.5 mg) increased the NaCl-induced potentiation of flunitrazepam binding in both nonstressed and stressed animals. Combined estradiol benzoate and progesterone treatment produced effects that were intermediate to those seen after injection of either steroid alone. The potentiation of flunitrazepam binding by NaCl observed in vehicle-treated stressed or progesterone-treated nonstressed animals was mimicked in vitro by addition to reaction test tubes of the neuroactive metabolite of progesterone, 3-hydroxy-5-pregnan-20-one (allopregnanolone). These results point to a significant role of ovarian hormones in modifying the stress response of the benzodiazepine receptor.     

雌激素对Azaserine诱导大鼠胰腺癌癌前病变DNA含量影响的实验研究

为了解雌激素对大鼠胰腺腺泡细胞癌癌前病变ＤＮＡ含量的影响,对雄性Ｗｉｓｔａｒ大鼠单次腹腔注射重氮乙酰丝氨酸（Ａｚａｓｅｒｉｎｅ）３０ｍｇ／ｋｇ,部分大鼠２个月后开始肌肉注射戊酸雌二醇０．１８ｍｇ．１００ｇ－１．２ｗ－１,４个月后实验结束,应用流式细胞分析术检测大鼠胰腺组织的ＤＮＡ含量等指标。与正常对照相比,单纯给予Ａｚａｓｅｒｉｎｅ的大鼠胰腺腺泡细胞癌癌前病变ＤＮＡ含量明显增加,异倍体率５５３％;经雌激素处理的大鼠胰腺腺胞细胞癌癌前病变ＤＮＡ含量亦明显增加,异倍体率４１０３％。结果表明：雌激素在一定程度上可抑制Ａｚａｓｅｒｉｎｅ诱导的大鼠胰腺腺泡细胞癌癌前病变的发生发展     

双炔失碳酯和双炔失碳醇抗生育作用的比较

本文比较双炔失碳酯和双炔失碳醇在小鼠中的抗生育效果,雌激素活性和与子宫胞浆雌激素受体的结合力,并研究双炔失碳酯的体内过程。结果发现,与双炔失碳醇相比,双炔失碳酯2β和17β位上的双丙酸酯并不明显增加其抗生育效果,也不明显改变其雌激素活性,但使双炔失碳酯在体外与子宫胞浆雌激素受体的结合力明显降低。结合[~(14)C]标记示踪实验结果,提示在体内,双炔失碳酯转化为双炔失碳醇而发挥其药理作用。     

雌激素受体在不同品系小鼠组织中的放射自显影定位和定量研究

本研究用氚—雌二醇和冰冻切片放射自显影方法观察了雌性LACA和C57BL小鼠下丘脑视叶前区神经核、垂体前叶、乳腺、胸腺、肝等器官雌激素受体的分布。结果表明,两个品系小鼠下丘脑视叶前区、垂体前叶细胞的标记串均在85％以上,标记细胞平均银颗粒数在19个以上。LACA品系小鼠乳腺上皮细胞标记率达96％,标记细胞平均银颗粒数12个。C57BL小鼠的标记率和银颗粒数分别为5％和5个。两个品系小鼠的肝和胸腺仅偶见个別细胞被标记。上述结果部分地解释了雌性激素(戊酸雌二醇和己酸孕酮)能诱发雌性LACA小鼠乳癌和C57BL小鼠的垂体肿瘤,而未能诱发C57BL小鼠乳癌的原因。雌激素受体的存在是个先决条件,但不是唯一的条件,可能还有其他因素的作用。因为两个品系小鼠的下丘脑视叶前区和LACA小鼠垂体前叶细胞均含有较多的雌激素受体,而雌性激素很少能诱发该组织发生肿瘤。     

兔输卵管平滑肌的肾上腺素受体与收缩活性

本文以离体兔输卵管平滑肌制备,比较输卵管各部(峡部和壶腹部)环肌和纵肌的肾上腺素受体效应及性激素状态的影响。经雌激素处理的兔输卵管峡部环肌和纵肌,对肾上腺素(Adr)、去甲肾上腺素(NA)和苯肾上腺素(PEP)均能产生浓度依赖性收缩反应,α-受体阻断剂则能对抗之。三种激动剂的pD_2值,顺序为Adr>NA>PEP。三种受体阻断剂对抗NA在兔输卵管峡部平滑肌引起收缩效应的pA_2值,顺序为酚妥拉明(Phen)≥哌唑嗪(Praz)>育亨宾(yoh)。β-受体阻断剂心得宁不影响Adr、NA和PEP所产生的收缩效应;心得安则对上述激动剂的兴奋效应具有明显非特异性抑制作用。孕激素处理的兔输卵管平滑肌,对不同浓度NA的收缩反应(包括E_(Amax))以及NA的pD_2值,均较雌激素处理组为低。提示孕激素可能降低α-激动剂与兔输卵管肾上腺素受体的亲和力,和/或减少受体数目。     

围绝经期妇女应用7-甲基异炔诺酮进行激素替代治疗顺应性调查

目的 探讨围绝经期妇女应用７－甲基异炔诺酮进行激素替代治疗的顺应性。方法 调查１３４例围绝经期处方７－甲基异炔诺酮者的用药状况,包括医嘱遵从性、中断比例及其原因以及体得改变、阴道出知、胃肠道反应等副作用。１３４例妇女平均５５．２岁,绝经６．７年,９７．０％因围绝经期症状就诊。结果 ９０．３％接受处方即开始治疗,治疗时间≤１年者５３例,治疗〉１年,≤３年者５５例,〉３年、≤５年者１０例,,５年者４全     

绝经妇女血浆一氧化氮、内皮素的水平及补充性激素后的变化

目的 探讨绝经妇女雌激素下后血浆一氧化氮（ＮＯ）与内皮素（ＥＴ）水平的变化,及服用结合雌激素加安宫黄体酮对ＮＯ、ＥＴ水平的影响。方法 选择７０例绝经妇女作为绝经组,２８例有围绝经期症状的妇女作为围绝经组,２６例月经周期正常的妇女作为正常月经组。绝经组中３０例服用结合雌激素加安宫黄体酮者为绝经１组,另外２０例服用碳酸钙治疗者为绝经２组,绝经１期及绝经２组用药时间均为６个月。以上各组均取静脉血测定ＮＯ