ThyagaRajan S, Quadri S K
Neuroendocrine Research Laboratory, Kansas State University, Manhattan, USA.
Endocrine. 1999 Jun;10(3):225-32. doi: 10.1007/BF02738621.
Previously, we have reported that L-deprenyl decreased the incidence of mammary tumors and pituitary tumors in old acyclic rats. The objective of the present study was to investigate the effects of L-deprenyl, a monoamine oxidase-B (MAO-B) inhibitor, treatment on the development and growth of tumors and on the metabolism of catecholamines and indoleamine in the medial basal hypothalamus (MBH) and the striatum (ST) of rats bearing 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors. Female Sprague-Dawley rats with DMBA-induced mammary tumors were injected (sc) daily with 0.25 mg or 5.0 mg of deprenyl/kg BW or the vehicle (saline; control) for 12 wk. Tumor diameter, tumor number, body weight, and feed intake were measured every week of the treatment period. Serum PRL and the concentrations of catecholamines, indoleamine, and their metabolites were measured by RIA and HPLC, respectively. Treatment with 5.0 mg deprenyl decreased the tumor diameter, tumor number, and serum prolactin (PRL) level. Although the body weight increased in all three groups, the body weight gain in the 5.0 mg group was smaller than that in the control and 0.25 mg groups. Deprenyl treatment had no effect on feed intake. The concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were decreased in the MBH and the ST, and the concentration of 5-hydroxyindoleacetic acid (5-HIAA) was decreased in the MBH of deprenyl-treated rats. Treatment with 5.0 mg deprenyl enhanced the concentrations of norepinephrine (NE) and serotonin (5-HT) in the MBH and in the ST, and the concentration of dopamine (DA) in the MBH. These results suggest that the suppression of the development and growth of DMBA-induced mammary tumors by chronic deprenyl treatment may be mediated through alterations in the synthesis and metabolism of catecholamines and indoleamine in the MBH and inhibition of PRL secretion.
此前,我们曾报道L-司来吉兰可降低老龄无发情周期大鼠乳腺肿瘤和垂体肿瘤的发生率。本研究的目的是探讨单胺氧化酶-B(MAO-B)抑制剂L-司来吉兰治疗对7,12-二甲基苯并蒽(DMBA)诱导的乳腺肿瘤大鼠内侧基底下丘脑(MBH)和纹状体(ST)中肿瘤发生发展、儿茶酚胺和吲哚胺代谢的影响。将患有DMBA诱导的乳腺肿瘤的雌性Sprague-Dawley大鼠每天皮下注射0.25mg或5.0mg司来吉兰/kg体重或赋形剂(生理盐水;对照),持续12周。在治疗期间每周测量肿瘤直径、肿瘤数量、体重和采食量。分别通过放射免疫分析(RIA)和高效液相色谱法(HPLC)测定血清催乳素(PRL)以及儿茶酚胺、吲哚胺及其代谢产物的浓度。5.0mg司来吉兰治疗可降低肿瘤直径、肿瘤数量和血清催乳素(PRL)水平。尽管三组体重均增加,但5.0mg组的体重增加幅度小于对照组和0.25mg组。司来吉兰治疗对采食量无影响。在接受司来吉兰治疗的大鼠中,MBH和ST中二羟基苯乙酸(DOPAC)和高香草酸(HVA)的浓度降低,MBH中5-羟吲哚乙酸(5-HIAA)的浓度降低。5.0mg司来吉兰治疗可提高MBH和ST中去甲肾上腺素(NE)和5-羟色胺(5-HT)的浓度以及MBH中多巴胺(DA)的浓度。这些结果表明,长期使用司来吉兰治疗抑制DMBA诱导的乳腺肿瘤的发生发展可能是通过改变MBH中儿茶酚胺和吲哚胺的合成与代谢以及抑制PRL分泌来介导的。