A CHARACTERIZATION OF ESTROGENS INFLUENCE ON ANTERIOR-PITUITARY ANDROGEN RECEPTOR - EFFECT OF BROMOCRIPTINE TREATMENT
A CHARACTERIZATION OF ESTROGENS INFLUENCE ON ANTERIOR-PITUITARY ANDROGEN RECEPTOR - EFFECT OF BROMOCRIPTINE TREATMENT
复制标题
DOI：
10.1159/000125691
复制
发表时间：
1991-01-01
影响因子：
4.1
通讯作者：
RODRIGUEZ, EW
中科院分区：
文献类型：
--
作者：
HANDA, RJ;RODRIGUEZ, EW
性腺类固醇的作用是通过与特定的细胞内受体结合来实现的。我们最近的研究表明，雌激素(E)治疗会增加垂体前叶(AP)胞浆雄激素受体(AR)的浓度，这可能反映了该组织对循环雄激素的敏感性增加。然而，慢性E治疗也会增加AP的重量和细胞数量。因此，进行了以下研究，以确定慢性E治疗后AP胞浆AR增加和AP体重增加之间的关系。将去性腺的Fischer 344(F344)大鼠植入5 mm的17-β-雌二醇硅胶胶囊。对照组动物被假植入。分别于E处理后第1、3、7、21天处死动物，称量AP腺体，检测胞浆AR和核雌激素受体(ER)含量。分别用H-3-双氢睾酮和H-3-雌二醇进行体外结合试验测定AR和ER。服用E的女性AP体重增加3天，男性增加7天(P<；0.05)。然而，接受E治疗的男性的AP体重始终显著低于女性(p<；0.05)。雌性大鼠肾上腺皮质AP胞浆AR含量(fmoL结合量/腺体)在给药后1d内显着增加，而雄性大鼠直到7d才显着增加。雌性和雄性的AP胞质AR含量分别在处理后7天和21天达到峰值。AP胞浆AR浓度(以每毫克胞浆蛋白表示)在E后3d达到高峰，此时无论男女都有显着的E效应。雌性大鼠经E处理21d后，AR浓度未见升高。这些数据表明，E治疗21天后AP重量的增加掩盖了E对每毫克蛋白表达的AP胞浆AR的影响。因此，我们通过同时给予溴隐亭(BR)来抑制E诱导的AP生长。在雌性F344大鼠体内植入BR恒释微丸(25 mg/只，21天)，同时给予BR和E。E治疗21天后处死动物。同时BR处理显著降低了E处理后的AP重量和血浆催乳素水平，增加了AR的浓度，但没有增加AR的含量(p<；0.05)。这些数据表明，暴露于E的AP中AR数目的增加不是AP生长的结果。这表明E诱导的AR增加与乳酸菌的增殖无关。
The action of gonadal steroids are mediated through the binding to specific intracellular receptors. Our recent studies have demonstrated that estrogen (E) treatment will increase the concentration of cytosolic androgen receptor (AR) in the anterior pituitary (AP) gland perhaps reflecting in increased sensitivity of this tissue circulating androgen. However, chronic E treatment also increases AP weight and cell number. Consequently, the following studies were performed to determine the relationship between increases in AP cytosolic AR and increases in AP weight following chronic E treatment. Gonadectomized male and female Fischer 344 (F344) rats were implanted with a 5-mm Silastic capsule of 17-beta-estradiol. Control animals were sham implanted. Animals were sacrificed at 1, 3, 7 and 21 days after the commencement of E treatment and AP glands were weighted and processed for cytosolic AR and nuclear estrogen receptor (ER) content. Ar and ER were determined by in vitro binding assays using H-3-dihydrotestosterone and H-3-estradiol, respectively. AP weight increased significantly by 3 days of E treatment in females and by 7 days in males (p < 0.05). However, AP weight of E-treated males was significantly less than females throughout (p < 0.05). Significant increases in AP cytosolic AR content (fmol bound/gland) were detected within 1 day of E treatment to female rats but not until 7 days in male rats. AP cytosolic AR content peaked at 7 days of E treatment in females and 21 days in males. AP cytosolic AR concentration (expressed as per milligram cytosol protein) peaked 3 days after E at which time there were significant E effects in both males and females. AR concentration was not elevated following 21 days of E treatment to female rats. These data suggested that the increases in AP weight following 21 days of E treatment were masking the effects of E on AP cytosolic AR when expressed on a per milligram protein basis. Consequently, we inhibited E-induced AP growth by the simultaneous administration of bromocriptine (BR). BR was administered concurrently with E to female F344 rats by the implantation of a constant release pellet of BR (25 mg/animal/21 days). Animals were sacrificed 21 days following E treatment. Concurrent BR treatment significantly reduced AP weight and plasma prolactin levels following E treatment and increased the concentration but not the content of AR (p < 0.05). These data demonstrate that increases in AR number in the AP as a result of E exposure is not a consequence of AP growth. This suggests that E-induced increases in AR are not related to lactotroph proliferation.