Megestrol acetate stimulates food and water intake in the rat: effects on regional hypothalamic neuropeptide Y concentrations.
Megestrol acetate, a synthetic progestogen, stimulates appetite through an unknown mechanism. We tested the hypothesis that it might act, at least in part, by stimulating the activity of hypothalamic pathways containing neuropeptide Y, a potent central appetite stimulant in rats. Administration of megestrol acetate (50 mg/kg/day, n = 8) for 9 days significantly increased food and water intake compared with untreated controls (n = 8). Treated rats showed significant (90-140%) increases in neuropeptide Y concentrations in the arcuate nucleus (where neuropeptide Y is synthesized), in the lateral hypothalamic area (through which arcuate neurones project) and in the medial preoptic area, ventromedial nucleus and dorsomedial nucleus. The latter are sites of neuropeptide Y release and sensitive to neuropeptide Y-induced hyperphagia. Megestrol acetate may therefore stimulate neuropeptide Y synthesis, transport and release, and this could contribute to its appetite-stimulating effects.
McCarthy
H D
HD
Department of Medicine, University of Liverpool, UK.
Crowder
R E
RE
Dryden
S
S
Williams
G
G
D000704:Analysis of Variance; D000818:Animals; D001066:Appetite / Q000187:drug effects; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004326:Drinking / Q000187:drug effects*; D004435:Eating / Q000187:drug effects*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008535:Megestrol / Q000031:analogs & derivatives* / Q000494:pharmacology; D019290:Megestrol Acetate; D009478:Neuropeptide Y / Q000378:metabolism*; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D009478:Neuropeptide Y; D008535:Megestrol; D019290:Megestrol Acetate