L-deprenyl inhibits tumor growth, reduces serum prolactin, and suppresses brain monoamine metabolism in rats with carcinogen-induced mammary tumors.
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.
ThyagaRajan
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Neuroendocrine Research Laboratory, Kansas State University, Manhattan, USA. sthyagarajan@som.llu.edu
Quadri
S K
SK
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004435:Eating; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D009638:Norepinephrine / Q000378:metabolism; D011388:Prolactin / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology* / Q000627:therapeutic use
D015306:Biogenic Monoamines; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; D006897:Hydroxyindoleacetic Acid; D011388:Prolactin; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid