垂体腺瘤雌孕激素受体的研究

目的:为了解垂体腺瘤的雌、孕激素受体分布情况及临床意义。方法:采用免疫组化方法检测了60例手术治疗的垂体腺瘤的雌激素受体(ER)、孕激素受体(PR),并结合内分泌功能分类和临床影像学检查进行研究。结果:研究表明,垂体腺瘤ER阳性率为77％,PR阳性率为67％。大的巨腺瘤ER、PR阳性率低于微腺瘤(PR间x~2=8.158,P=0.017<0.05)。细胞生长活跃的腺瘤ER、PR常阴性。不同功能类型的垂体腺瘤ER、PR阳性率亦不同。结论:研究提示ER、PR与垂体腺瘤的分化侵袭有关,ER、PR检测可能是垂体腺瘤选择治疗和评估预后的一项指标。     

脑膜瘤细胞性激素受体表达与其中心供血动脉起源的关系

目的探讨脑膜瘤细胞性激素受体的表达及其与肿瘤中心供血动脉起源的关系。方法对43份脑膜瘤标本行免疫组化检测,观察性激素受体表达情况,分析其与中心供血动脉起源的关系。结果脑膜瘤细胞雌激素受体(ER)表达与肿瘤中心供血动脉起源无明显相关性;肿瘤中心供血动脉源于颈外动脉组时其孕激素受体(PR)和雄激素受体(AR)阳性率(26.9%,23.1%)明显低于颈内动脉组(88.9%,77.8%)及颈内外动脉联合组(87.5%,87.5%)(均P<0.05),而颈内动脉组与颈内外动脉联合组间PR和AR阳性率差异无显著性。结论脑膜瘤细胞PR、AR阳性表达率高可能与肿瘤中心供血动脉的起源有关。     

Psychosocial correlates of progesterone receptors in breast cancer

Background: The diagnosis of cancer may lead to psychological distress with anxiety and depression as the most prevalent symptoms. Several investigators have found a correlation between psychosocial factors and tumor levels of estrogen receptors and progesterone receptors (PRs) while others have not. The aim of this study was to investigate demographic characteristics and severity of depression and anxiety as expressed by the Hospital Anxiety and Depression (HAD) scale of patients with high or low PR expression in breast cancers. Methods: Two hundred and seventy‐eight patients with primary breast cancer were divided into two subgroups according to PRs expressed in breast cancers. Results: The subgroup of patients with PR‐negative breast cancers expressed depression, as measured by the HAD scale, to a smaller degree (4.7±4.1) than the subgroup of patients with PR‐positive breast cancers (5.8±4.1). The difference was rather small but still statistically significant (t=2.1, df=236.7, P<.05). In contrast, we did not observe any correlation between anxiety and PR status. Differences between the subgroups according to family history of mental disorders were observed (χ²=4.7, df=1, P<.05). In the subgroup of patients with PR‐negative breast cancers; 13% of patients had a family history of mental disorders compared with 23% of patients with PR‐positive breast cancers. Conclusions: Depression expressed by patients with primary breast cancers could be influenced by the PR status of the tumors; however, other factors such as cancer treatment and family history of mental disorders could also be important. Depression and Anxiety, 2009. © 2008 Wiley‐Liss, Inc.     

Androgen and estrogen receptors in adult hamster brain

Both androgen and estrogen receptors are present in the hypothalamus-preoptic area and remaining ‘brain’ regions of gonadectomized adult male and female hamsters. No quantitative or qualitative sex differences are detectable in either receptor system. According to all biochemical criteria tested, both receptors are qualitatively similar to those present in mouse and rat brain. However, there are striking species differences in both the relative concentration and distribution of both androgen and estrogen receptors in hamster brain compared to mouse and rat brain.     

Immunohistochemical expression of progesterone and estrogen receptors in meningiomas

In this study we present results of investigations of progesterone and estrogen receptors in most frequent, WHO grade I histological types of meningiomas (meningothelial, fibrous, and transitional) and in atypical--WHO grade II variant of these tumors. Samples from 64 tumors were examined. The cohort consisted of 46 WHO grade I (21 transitional, 13 fibrous and 12 meningothelial histologic variants) and of 18 atypical meningiomas. Apart from immunohistochemical examination of progesterone and estrogen receptors, MIB 1 labeling index was estimated. Positive immunoreaction for progesterone receptors was found in 100% meningothelial, 95% transitional, 46% fibrous and 78% atypical variant of meningiomas. Intensity of immunoreaction was stronger in grade I than in grade II tumors. Immunoexpression of estrogen receptors was found in 48% of the investigated meningiomas. No correlation was stated between WHO grade I and grade II tumors, and between meningothelial, transitional and fibrous variants of the neoplasms.     

The participation of histaminergic receptors of the rostral hypothalamus on the tonic release of luteinizing hormone (LH) in adult spayed rats under estrogen and progesterone treatment

Summary The influence of histaminergic sites in the preoptic-anterior hypothalamic area (POA-AHA) on the basal release of luteinizing hormone (LH) under a continuous regimen of estradiol, progesterone, or both was studied in ovariectomized rats. Different groups of animals were subjected to the following experimental schedule: at day 1, rats received a s.c. silastic implant filled with oil, estradiol, progesterone, or estradiol plus progesterone. Seven days later (day 7), animals were implanted into the POA-AHA with microinjection cannulae. At day 8 and 9, the different groups of rats were microinjected with 1 l of saline solution containing 35 nMol of pyrilamine or metiamide, or 20 nMol of alpha-fluoro-methyl-histidine. At day 10, blood samples were taken through a permanent jugular cannulae implanted in situ the day before. LH concentrations were determined in plasma by RIA. Results showed that the increase of LH plasma levels induced by the ovariectomy was inhibited by the estrogen implant, as expected. Treatment of metiamide or alpha-fluoro-methyl-histidine did not affect the pattern of LH secretion. Nevertheless, treatment of metiamide induced a transient increase in the gonadotropin concentrations that extended for two hours (16:00 and 17:00 H). No change in LH plasma levels was observed in rats bearing the progesterone implant. Treatments (pyrilamine, metiamide, or alpha-fluoro-methyl-histidine into the POA-AHA) had no effect. The transient increase in the hormone levels observed in rats treated with pyrilamine in the estrogen-implanted rats was absent in rats bearing the estrogen-progesterone implant. Present data support the concept that histamine is involved in the POA-AHA to control the pituitary LH release and emphasize the role of plasma estrogen to facilitate the expression of HA receptors.     

Aromatization of androgen to estrogen by cultured turtle brain cells

Cells obtained from turtle forebrain can be maintained in culture for at least 3 weeks. The cells are capable of aromatizing [³H]androstenedione and [³H]testosterone to estrone and estradiol and several C-19 metabolites. There are marked differences in the quality and quantity of the products formed from the two substrates. Conditions in living cells favor accumulation of 17-hydroxylated steroids. Aromatase activity as measured by estrogen yield increases with time in culture. Estrogen content of 14-day-old cultures may be enhanced or reduced by addition of natural or synthetic steroids. This system may provide a model for studying the regulation of brain aromatization, an essential step in the expression of androgen action on certain behavioral and neuroendocrine responses.     

Immunohistochemical expression of apoptosis regulating proteins and sex hormone receptors in meningiomas

Meningiomas are well known to be responsive to estrogen/progesterone stimulation, and their expression of estrogen/progesterone receptor (ER/PR) has been documented. On the other hand, there are several reports studying expression of apoptosis‐regulating proteins (ARPs) and its significance in meningiomas. However, very limited published information exists on the exact relation among sex hormone receptor status, apoptosis, proliferation index (PI), and histological grade in meningiomas. A total of 57 cases of non‐malignant meningiomas were selected, and histologically reviewed and graded (WHO grades 1, 2). All these cases were immunostained for ER, PR, Ki‐67, and ARPs including bax, bcl‐2, and bcl‐xL. Sections were graded semiquantitatively for intensity and extent of immunostaining. PI was expressed as a percentage of Ki‐67 positive tumor cells. Expression of bax, bcl‐2, bcl‐xL, ER, and PR was seen in 100, 35.1, 24.6, 10.4, and 87.2% of cases, respectively. Bax was expressed diffusely and strongly, while Bcl‐2 tended to be expressed weakly and focally. Bcl‐xL appeared to be expressed relatively strongly and diffusely in a small subset. There was significantly higher PI as well as expression of PR in grade 1 group than in grade 2 group. A weak negative correlation was observed between Bcl‐2 and PR (r =?0.472, P < 0.0014). Given high‐level expression of pro‐apoptotic bax, which seems to be constitutionally expressed, in contrast to low‐level expression of antiapoptotic bcl‐2 and bcl‐xL, other antiapoptotic proteins may involve the proliferation of meningiomas. A significant negative relation exists between PR and Bcl‐2 in meningiomas, which might have some biological and clinical significance.     

马桑内酯激活星形胶质细胞条件培养液对大脑皮质及海马神经元雌、孕激素受体的影响

BACKGROUND： Coriaria lactone-activated astrocytes released bioactive substances that eventually caused epilepsy.
OBJECTIVE： It has been suggested that activated astrocytes alter the expression of the estrogen receptor and progesterone receptor by releasing bioactive substances during epilepsy, thereby affecting neuronal activity in the brain. This study was designed to observe the expression of the estrogen receptor and the progesterone receptor in rat brain following lateral ventricle injection of coriaria lactone-activated, astrocyte-conditioned medium.
DESIGN AND SETTING： This immunohistochemical, randomized, controlled, animal study was conducted at the Department of Pathology, Hospital Affiliated to Binzhou Medical College, China.
MATERIAL： Coriaria lactone was provided by Huaxi Pharmaceutical Factory, China. METHODS： Forty adult, healthy, male, Sprague Dawley rats were randomly assigned into two groups. Astrocyte-conditioned medium （10 μ L） was injected into rat lateral ventricle in the control group （n = 8）. Coriaria lactone-activated, astrocyte-conditioned medium （10 μL） was infused into the rat lateral ventricle in the coriaria lactone group （n = 32）. At 2, 4, 8 and 12 hours following injection, rats were sacrificed and subjected to immunohistochemistry. Eight rats were studied at each time point.
MAIN OUTCOME MEASURES： Behavioral changes were observed in rats of both groups. Expression of the estrogen receptor and the progesterone receptor in rat cortical and hippocampal neurons was measured using immunohistochemistry.
RESULTS： Four hours after injection, estrogen receptor levels in rat cortical and hippocampal neurons were significantly higher in the coriaria lactone group than in the control group （P 〈 0.05）. Progesterone receptor levels were significantly lower in the coriaria lactone group than in the control group （P 〈 0.05）. Seizures were not observed in the control group. In the coriaria lactone group, convulsions appeared 30 minutes after injection; seizures reached grade Ⅲ at 45 minutes rat behavior was nearly normal at 2 hours.
CONCLUSION： Activated astrocytes can induce seizures in the rat by enhancing estrogen receptor expression and decreasing progesterone receptor expression in cerebral cortical and hippocampal neurons.     

Progesterone treatment of adult male rats suppresses arginine vasopressin expression in the bed nucleus of the stria terminalis and the centromedial amygdala

The steroid sensitive vasopressin cells of the bed nucleus of the stria terminalis (BST) and centromedial amygdala (CMA) are involved in numerous behavioural and physiological functions. These cells are known to be greatly influenced by gonadal steroids. Castration reduces and testosterone replacement restores arginine vasopressin (AVP)-immunoreactive (-ir) labelling and AVP mRNA expression in the BST and CMA. Gonadal steroids appear to act directly in AVP-expressing cells within the BST and CMA, because the majority of AVP-ir cells in these areas contain oestrogen and androgen receptor immunoreactivity. Recently, we have localised progestin receptor immunoreactivity in virtually all of the AVP-ir cells in the BST and CMA. To understand the role played by progestin receptors in AVP cells within the BST and CMA, we treated male rats with 1 mg of progesterone or oil for 5 days, and then examined AVP immunoreactivity within the brain. We found that progesterone decreased AVP-ir labelling within the BST and CMA, as well as in two of the projection sites of these cells, the lateral septum and lateral habenula. Progesterone treatment did not alter testosterone secretion from the testes, nor did it alter adult male sexual behaviour. These data illustrate an additional mechanism by which the AVP cells in the BST and CMA can be regulated. These data also suggest that progesterone may act in the male brain to influence behaviours that are AVP-dependent.     

Translational mobility of Concanavalin A receptors in normal and neoplastic glial cells

Summary The dynamics of cell-associated Concanavalin A (Con A) in astrocytes of the newborn rat (RNA), the rat glioma (AC), and the human glioblastoma (GB) were studied in vitro by fluorescence and electron microscopy. Con A receptors on the cell surface were seen usually as a continuous thin layer, and Con A accumulations in fluorescence microscopy were actually Con A receptors on complicatedly infolded cell membrane and collection of Con A pinosomes. No capping occurred in the three types of glial cells. The translational movement of Con A receptors on the cell surface was rapid in the AC, slow in the RNA, and intermediate in the GB, and partly associated with Con A internalization. Con A pinosomes were more numerous in the RNA compared with those in the AC and the GB. Colchicine accelerated the translational mobility of surface Con A receptors more markedly in the AC and the GB than in the RNA. The translational movement Con A receptors, when treated with cytochalasin B, was retarded in the RNA and the GB and rather accelerated in the AC. Con A pinosomes were decreased in the three types of glial cells by treatment with colchicine or cytochalasin B.     

Ultrastructural localization of extranuclear progestin receptors in the rat hippocampal formation

Progesterone's effects on hippocampus-dependent behavior and synaptic connectivity maybe mediated through the progestin receptor (PR). Although estrogen induces PR mRNA and cytosolic PR in the hippocampus, nuclear PR immunoreactivity is undetectable by light microscopy, suggesting that PR is present at extranuclear sites. To determine whether this is the case, we used immunoelectron microscopy to examine PR distribution in the hippocampal formation of proestrus rats. Ultrastructural analysis revealed that PR labeling is present in extranuclear profiles throughout the CA1 and CA3 regions and dentate gyrus, and, in contrast to light microscopic findings, in nuclei of a few pyramidal and subgranular zone cells. Most neuronal PR labeling is extranuclear and is divided between pre- and postsynaptic compartments; approximately 30% of labeled profiles were axon terminals and 30% were dendrites and dendritic spines. In most laminae, except in CA3 stratum lucidum, about 15% of PR-immunoreactive profiles were unmyelinated axons. In stratum lucidum, where the mossy fiber axons course, more than 50% of PR-labeled profiles were axonal. The remaining 25% of PR-labeled profiles were glia, some resembling astrocytes. PR labeling is strongly dependent on estrogen priming, insofar as few PR-labeled profiles were detected in ovariectomized, oil-replaced females. Synapses formed by PR-labeled terminals were predominantly asymmetric, consistent with a role for progesterone in directly regulating excitatory transmission. These findings suggest that some of progesterone's actions in the hippocampal formation may be mediated by direct and rapid actions on extranuclear PRs and that PRs are well positioned to regulate progesterone-induced changes at synapses.     

Distribution of androgen receptor mRNA expression in vocal,auditory, and neuroendocrine circuits in a teleost fish

Across all major vertebrate groups, androgen receptors (ARs) have been identified in neural circuits that shape reproductive‐related behaviors, including vocalization. The vocal control network of teleost fishes presents an archetypal example of how a vertebrate nervous system produces social, context‐dependent sounds. We cloned a partial cDNA of AR that was used to generate specific probes to localize AR expression throughout the central nervous system of the vocal plainfin midshipman fish (Porichthys notatus). In the forebrain, AR mRNA is abundant in proposed homologs of the mammalian striatum and amygdala, and in anterior and posterior parvocellular and magnocellular nuclei of the preoptic area, nucleus preglomerulosus, and posterior, ventral and anterior tuberal nuclei of the hypothalamus. Many of these nuclei are part of the known vocal and auditory circuitry in midshipman. The midbrain periaqueductal gray, an essential link between forebrain and hindbrain vocal circuitry, and the lateral line recipient nucleus medialis in the rostral hindbrain also express abundant AR mRNA. In the caudal hindbrain‐spinal vocal circuit, high AR mRNA is found in the vocal prepacemaker nucleus and along the dorsal periphery of the vocal motor nucleus congruent with the known pattern of expression of aromatase‐containing glial cells. Additionally, abundant AR mRNA expression is shown for the first time in the inner ear of a vertebrate. The distribution of AR mRNA strongly supports the role of androgens as modulators of behaviorally defined vocal, auditory, and neuroendocrine circuits in teleost fish and vertebrates in general. J. Comp. Neurol. 518:493–512, 2010. © 2009 Wiley‐Liss, Inc.     

No correlation of depression and anxiety to plasma estrogen and progesterone levels in patients with premenstrual dysphoric disorder

A number of studies have demonstrated the correlation of depression and anxiety to estrogen and progesterone in premenstrual dysphoric disorder (PMDD), but the findings are still controversial. The purpose of this study was to determine the correlation of depression and anxiety to estrogen and progesterone concentrations in blood plasma in Taiwanese women with PMDD. A total of 43 women who met the 4th edition of the Diagnostic and Statistical Manual diagnostic criteria for PMDD were enrolled in this study. Blood samples were obtained for determination of estrogen and progesterone levels, and depression and anxiety ratings were summed for each subject during one menstrual cycle to obtain a premenstrual result (2-6 days before menses) and a postmenstrual result (menstrual cycle days 7-11). Anxiety was assessed using the 14-item Hamilton Anxiety Scale-A and was also assessed by the patients themselves using the Trait Anxiety Inventory. Depression was rated using the 21-item Hamilton Anxiety Scale-D. Calculations were made to determine the relationships between hormonal changes and mood changes. There were no statistically significant correlations between depression or anxiety ratings and estrogen or progesterone concentrations.     

Overexpression of mdm2 and p53 and association with progesterone receptor expression in benign meningiomas

The progesterone receptor is frequently found expressed in meningiomas at robust levels. As several studies of breast and endometrial tumors have shown an inverse correlation between progesterone receptor expression and p53 overexpression, we sought to determine if a similar relationship existed in meningiomas. As p53 may also be inactivated by the overexpression of mdm2, we examined a cohort of 90 benign meningiomas immunohistochemically for the presence of the progesterone receptor as well as overexpression of p53 and mdm2. The progesterone receptor was detected in 67% (61/90) of cases, while p53 and mdm2 overexpression were detected in 14% (13/90) and 46% (42/90) of cases, respectively. An absolute correlation was observed between the overexpression of nuclear mdm2 and overexpression of the progesterone receptor, with nuclear mdm2 overexpression being confined to progesterone receptor‐positive tumors (P = 0.001). While p53 overexpression was not associated with progesterone receptor expression, a combination of mdm2 overexpression and/or p53 overexpression was significantly associated with the presence of the progesterone receptor (P = 0.025). These results suggest the existence of a novel relationship between p53 (and its regulatory control) and the presence of the progesterone receptor and, as such, may have fundamental consequences in developing progesterone receptor‐targeted therapies for meningiomas.     

Colocalization of androgen, estrogen and cholinergic receptors on cultured astrocytes of rat central nervous system

By means of immunohistochemical and electrophysiological methods, we have investigated the presence of androgen receptors on astrocytes in explant and primary cultures from various regions of rat central nervous system. Our studies have shown that a great number of astrocytes and neurones express androgen receptors as recognized by a specific monoclonal antibody. Immunoreactivity was mainly distributed over the soma of the astrocytes, the nuclei being intensely stained. In contrast, glial processes were only faintly stained or not stained. Double-immunostaining studies have provided evidence for a colocalization of androgen and estrogen alpha- and beta-receptors on many astrocytes. Furthermore, there was also a coexistence of glial androgen receptors with cholinergic muscarinic and nicotinic sites. Our immunohistochemical findings are supported by electrophysiological investigations demonstrating that 5alpha-androstan, 17beta-estradiol as well as the cholinergic agonists muscarine and nicotine caused hyperpolarizations on the same astrocytes. Our studies suggest that there is a coexistence of functional receptors for androgen, estrogen as well as for the cholinergic agonists on glial cells. Further investigations are needed to elucidate the physiological role of glial androgen, estrogen and cholinergic receptors and to define their function in neurodegenerative diseases.     

Alteration of sensitivity to progesterone facilitation of lordosis in guinea pigs by modulation of hypothalamic progestin receptors

In order to delineate further the role of the progestin receptor system in the hypothalamus-preoptic area in the regulation of lordisis in female guinea pigs, we injected estradiol benzoate and progesterone in various regimens that result in sensitivity to, desensitization to, or restoration of sensitivity to progesterone-facilitation of lordosis. We attempted to correlate the effectiveness of progesterone to facilitate lordosis with the effectiveness of progesterone to cause accumulation of nuclear progestin receptors measured by an in vitro [³H]R 5020 binding assay.A progesterone injection 40 h after an estradiol benzoate injection in ovariectomized guinea pigs resulted in lordosis in 83% of the animals, caused a 30% depletion of cytoplasmic progestin receptors and a 200% increase in the concentration of nuclear progestin receptors 4 h after injection compared with control animals. By 24 h after the injection, after the period of sexual receptivity had terminated, the concentration of nuclear progestin receptors was no longer elevated, and the concentration of cytoplasmic progestin receptors was decreased to a level 55% lower than control animals. This depression was due to a decrease in the concentration of binding sites, not to in vitro competition of the injected progesterone with the [³H]R 5020 because similar results were obtained with cytosol in which progesterone had been removed by gel filtration prior to incubation. These progesterone-injected guinea pigs did not respond to a second progesterone injection 24 h after the first (64 h), and the injection resulted in 70% fewer nuclear progestin receptors than in oil-injected controls. This decreased accumulation appears to be due to the decreased level of cytoplasmic progestin receptors brought about by the first progesterone injection.Estradiol benzoate injected concurrently with the first progesterone injection restored behavioral sensitivity to the second progesterone injection and caused 160% greater accumulation of nuclear progestin receptors in response to the second progesterone injection than control animals that had received only progesterone. The increased concentration of nuclear progestin receptors in the estradiol-injected animals appear to be due to increased availability of cytoplasmic progestin receptors.It seems that estradiol increases and progesterone decreases the concentration of cytoplasmic progesterone receptors in hypothalamus-preoptic area such that a subsequent injection of progesterone results in a high or low concentration of nuclear progestin receptors. The accumulation of sufficient nuclear progestin receptors in response to the progesterone injection may be a requirement in the process by which progesterone facilitates lordosis in estradiol-primed rodents.