Matera C, Wardlaw S L
Department of Obstetrics and Gynecology, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
Neuroendocrinology. 1993 Nov;58(5):493-500. doi: 10.1159/000126582.
Previous studies have shown that POMC mRNA and peptide levels are increased in the medial basal hypothalamus (MBH) of the chronically castrated rat and are suppressed with sex steroid replacement. In a parallel time course, hypothalamic dopamine turnover similarly changes after chronic castration and sex steroid replacement. In this study we have examined the effects of dopamine on POMC in the MBH and questioned whether the increase in dopamine activity which occurs in the MBH of chronically castrated rats is responsible for the stimulation of POMC seen under these conditions. We have therefore measured POMC gene expression and peptide content in the MBH of chronically castrated male and female rats in response to the dopamine antagonist haloperidol, and in intact or sex steroid replaced animals in response to the dopamine agonist pergolide. Adult male and female rats were studied 3-4 weeks after castration with and without testosterone (T) or estradiol (E2) replacement. POMC mRNA was measured by a solution hybridization S1 nuclease protection assay; beta-endorphin (beta-EP) and alpha-MSH were measured by RIA. In the first study 4 groups of ovariectomized (OVX) rats were treated with saline, haloperidol, E2 or E2 + pergolide. The mean POMC mRNA concentration in the MBH was 0.85 +/- 0.04 pg/microgram RNA in the saline group and decreased to 0.62 +/- 0.06 pg/microgram with haloperidol (p < 0.01). A similar decrease to 0.53 +/- 0.03 pg/microgram was seen with E2 (p < 0.01); pergolide however prevented the E2 induced decrease in POMC mRNA. In the second study ORCX rats received saline or haloperidol and sham-ORCX rats received saline or pergolide.(ABSTRACT TRUNCATED AT 250 WORDS)
先前的研究表明，在长期阉割的大鼠内侧基底下丘脑（MBH）中，促黑素细胞激素原（POMC）信使核糖核酸（mRNA）和肽水平会升高，而用性类固醇替代后则会受到抑制。在平行的时间进程中，慢性阉割和性类固醇替代后，下丘脑多巴胺周转率也会发生类似变化。在本研究中，我们检测了多巴胺对MBH中POMC的影响，并质疑长期阉割大鼠MBH中出现的多巴胺活性增加是否是这些条件下观察到的POMC刺激的原因。因此，我们测量了长期阉割的雄性和雌性大鼠MBH中POMC基因表达和肽含量，以响应多巴胺拮抗剂氟哌啶醇，以及完整或性类固醇替代动物对多巴胺激动剂培高利特的反应。成年雄性和雌性大鼠在阉割后3 - 4周接受研究，有或没有睾酮（T）或雌二醇（E2）替代。通过溶液杂交S1核酸酶保护试验测量POMC mRNA；通过放射免疫分析（RIA）测量β-内啡肽（β-EP）和α-促黑素（α-MSH）。在第一项研究中，4组卵巢切除（OVX）大鼠分别用生理盐水、氟哌啶醇、E2或E2 + 培高利特治疗。生理盐水组MBH中POMC mRNA的平均浓度为0.85±0.04 pg/μg RNA，氟哌啶醇处理后降至0.62±0.06 pg/μg（p < 0.01）。E2处理后也出现类似下降，降至0.53±0.03 pg/μg（p < 0.01）；然而，培高利特阻止了E2诱导的POMC mRNA下降。在第二项研究中，去势大鼠接受生理盐水或氟哌啶醇，假去势大鼠接受生理盐水或培高利特。（摘要截断于250字）
