卵子赠送妊娠后激素替代治疗剂量与时间的初步探讨

为了探讨卵子赠送妊娠后胎盘类固醇激素产生的时间;外源性激素替代治疗的合理剂量和疗程;药物减量和停药的指征。采用低剂量类固醇激素替代与卵子赠送技术使５例卵巢早衰患者、２例绝经前期患者获得单胎妊娠,在孕４～１２周应用放射免疫法连续测定血清雌二醇（Ｅ２）、雌三醇（Ｅ３）及孕酮（Ｐ）水平,并与５例正常单胎妊娠同期水平比较。结果：７例卵子赠送单胎妊娠均于孕１２周安全停药,均足月分娩。Ｅ２和Ｐ水平分别于孕５和６周开始上升,孕６和７周明显高于孕４周基础值（Ｐ分别＜０．００１和＜０．００２）。孕７～１２周血清Ｅ２水平与正常单胎妊娠组同期水平相似。血清Ｅ３水平从孕６～７周开始升高,孕１０～１１周稳定于２０～３０μｇ／Ｌ范围,与正常单胎妊娠组无区别。结论：胎盘组织从孕５～７周开始分泌Ｅ２和Ｐ进入母体外周血,提示胎盘功能出现,可考虑药物逐渐减量。Ｅ３从孕１０周起稳定在中期妊娠水平,提示黄体与胎盘功能交替完成,此时应停用外源性激素。     

甲状腺肿瘤组织中雌、孕激素受体表达及临床意义

目的　探讨甲状腺肿瘤组织中雌激素受体 (ER)、孕激素受体 (PR)的表达与肿瘤浸润转移的关系。方法　应用SABC免疫组化法 ,对 10 0例甲状腺癌及 2 8例甲状腺良性肿瘤中ER、PR进行检测。结果　甲状腺癌中ER、PR阳性表达分别为 6 7.0 %和 6 2 .0 % ,均与细胞分化程度、组织学类型有关 ,但其阳性表达与年龄、性别无关。ER、PR在无淋巴结转移组的甲状腺癌中阳性率为 75 .4%和 70 .5 % ,显著高于有转移组的 5 3 .8%和 48.7% (P <0 .0 5 )。结论　ER、PR可作为判断肿瘤分化程度及预后的指标     

乳腺癌原发灶与转移灶内雌激素受体及孕激素受体水平变化分析

目的 分析乳腺癌原发灶与转移灶内雌激素受体(ER)及孕激素受体(PR)水平变化的临床意义.方法 82例存在远处转移灶或腋窝淋巴结转移灶的乳腺癌患者,其中远端转移灶患者40例,腋窝淋巴结转移灶患者42例.切除患者局部组织,获取乳腺癌原发灶及转移灶组织,采用免疫组织化学(免疫组化)方法检测病灶中ER、PR水平.分析比较原发...     

Breast cancer in young women and prognosis: How important are proliferation markers?

AimCompared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis.MethodsDistant disease-free survival (DDFS) was studied in 504 women aged <40 years and 383 women aged ≥40 years from a population-based cohort. Information on patient characteristics, treatment and follow-up was collected from medical records. Tissue microarrays were produced for analysis of oestrogen receptor, progesterone receptor (PR), Her2, Ki-67 and cyclins.ResultsYoung women with luminal tumours had significantly higher expression of Ki-67 and cyclins. Proliferation markers were prognostic only within this subtype. Ki-67 was a prognostic indicator only in young women with luminal PR+ tumours. The optimal cut-off for Ki-67 varied by age. High expression of cyclin E1 conferred a better DDFS in women aged <40 years with luminal PR− tumours (hazard ratio [HR] 0.47 [0.24–0.92]). Age <40 years was an independent risk factor of DDFS exclusively in women with luminal B PR+ tumours (HR 2.35 [1.22–4.50]). Young women with luminal B PR− tumours expressing low cyclin E1 had a six-fold risk of distant disease compared with luminal A (HR 6.21 [2.17–17.6]).ConclusionsThe higher expression of proliferation markers in young women does not have a strong impact on prognosis. Ki-67 is only prognostic in the subgroup of young women with luminal PR+ tumours. The only cyclin adding prognostic value beyond subtype is cyclin E1. Age is an independent prognostic factor only in women with luminal B PR+ tumours.     

Neuroendocrinology of childbirth and mother–child attachment: The basis of an etiopathogenic model of perinatal neurobiological disorders

This review focuses on the neuroendocrine mechanisms in the mother and the newborn that are involved in the generation and consolidation of mother–child attachment. The role that different hormones and neurotransmitters play on the regulation of these mechanisms during parturition, the immediate postpartum period and lactation is discussed. Interferences in the initiation of mother–child attachment may have potential long-term effects for the behavior and affection of the newborn. Therefore, the possible consequences of alterations in the physiological neuroendocrine mechanisms of attachment, caused by elective Cesarean section, intrapartum hormonal manipulations, preterm delivery, mother–infant postpartum separation and bottle-feeding instead of breastfeeding are also discussed.     

Circulating levels of anticonvulsant metabolites of progesterone in women with partial epilepsy in the intercritical phase

The 3alpha-hydroxy metabolites of progesterone (P), 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone, A-PREG) and 3alpha-hydroxy-5beta-pregnan-20-one (pregnanolone, PREG), have been found to be among the most potent ligands of gamma-aminobutyric (GABA)-A receptors; in experimental animals, they have been found to have anxiolytic, hypnotic and anticonvulsant effects. Similar to those of the benzodiazepines and barbiturates that interact with GABA-A receptors. The present study was undertaken to determine plasma A-PREG and PREG concentrations in the luteal phase in women with partial epilepsy, in order to determine if an impaired metabolism of P occurs in this convulsive disorder. We measured plasma P, A-PREG and PREG levels in 15 women with partial epilepsy in the intercritical phase, and in 15 age-matched healthy women, during the luteal phase of the ovarian cycle (22nd-24th day). The mean plasma ± S.E. A-PREG levels (three blood samples) were 0.7±0.6 ng/ml in the epileptic women and 0.5±0.2 ng/ml in controls, with no significant difference between the two groups (p=NS); the PREG levels were also similar (1.4±1 ng/ml and 1±1.1 ng/ml, respectively: p=NS). A significant correlation was found between P levels and both A-PREG and PREG levels (r=0.72, p<0.001 and r=0.79, p<0.001, respectively). There were no significant differences between the two groups in terms of serum adrenocorticotropic hormone, cortisol, dihydroepiandrosterone-sulfate, follicle stimulating hormone, prolactin, luteinizing hormone or estradiol levels.This work was partially supported by grants from the Ministero della Università e della Ricerca Scientifica e Tecnologica (M.U.R.S.T. 40% and 60%).     

Regulation of expression of cytochrome P-450 2D mRNA in rat brain with steroid hormones

Cytochrome P-450 2D is a subfamily of the cytochrome P-450-dependent mixed function oxidase system which is widely distributed in the various tissues of mammals. Sex steroid hormones have been shown to affect the expression of CYP2D in rat brain. Testosterone treatment of ovariectomized female rats elicits a dramatic increase in CYP2D expression, estrogen treatment brings about a modest increase in brain CYP2D expression and reduces the increase in CYP2D expression elicited with testosterone when the two hormones are coadministered. Polymerase chain reaction (PCR) has been used in our laboratory, as well as other laboratories, to measure the low levels of message for various P-450s in brain [Hodgson, A.V., White, T.B., White, J.W., Strobel, H.W., 1993. Expression analysis of the mixed function oxidase system in rat brain by the polymerase chain reaction. Mol. Cell. Biochem. 120, 171–179; Omiecinski, C.J., Redlich, C.A., Costa, P., 1990. Induction and developmental expression of cytochrome P450IA1 messenger RNA in rat and human tissues: detection by the polymerase chain reaction. Cancer Res. 50, 4315–4321]. In this study, competitive PCR (cPCR) approaches have been used to determine effects of progesterone and testosterone on CYP2D expression levels in brains of intact and ovariectomized female rats. When administered for seven treatments, testosterone significantly increases the expression of CYP2D in brain from intact female rats, while repeated treatment with progesterone elicits the opposite effect. Coadministration of testosterone and progesterone causes an intermediate effect such that the net result is an increase in expression only slightly above control levels. Interestingly, when ovariectomized female rats treated with testosterone and progesterone are used as a source of brain tissue for RNA preparation a similar trend toward an intermediate value is seen but the net result is an expression level of CYP2D below the control value. This approach utilizes cPCR to analyze the levels of CYP2D mRNA, semi-quantitatively and quantitatively, in the brains of female intact and ovariectomized Sprague–Dawley rats treated with testosterone, progesterone, a combination of the two or corn oil.     

卵巢中去甲肾上腺素含量和血清雌、孕激素水平相互关系的研究

利用荧光分光光度法测定了动情周期中大鼠与未成熟鼠卵巢组织中的NE含量,同时用放射免疫法测定其血中雌、孕激素的水平.结果表明动情周期中大鼠卵巢NE含量与血清雌、孕激素水平均有周期性波动,其中NE含量变化与孕激素水平变化间有显著的直线依存关系.未成熟鼠的NE与性激素含量明显低于成年大鼠.作者认为,性成熟前卵巢NE含量低,其内分泌功能处于相对静止状态;而性成熟后,NE含量增多,可能促进卵巢内孕激素的合成     

Influence of phenobarbital and various steroids on CCl4 hepatotoxicity

In rats, pretreatment with progesterone, triamcinolone or phénobarbital increased mortality, liver damage and triglyceride accumulation induced by CCl₄. Antimineralocorticoids (e.g., spironolactone, SC-11927), anabolic steroids (e.g., ethylestrenol, norbolethone, oxandrolone), estradiol and desoxycorticosterone proved to be ineffective in this respect. SKF525-A administered alone or in combination with progesterone or phenobarbital did not significantly affect CCl₄ hepatotoxicity.This work was supported by grants from the Ministère de la Santé, Quebec and the Medical Research Council of Canada (Block Term Grant MT-1828).