Effects of long-term hormone replacement and of tibolone on choline acetyltransferase and acetylcholinesterase activities in the brains of ovariectomized, cynomologus monkeys.
We examined long-term effects of low and high doses of tibolone, conjugated equine estrogens, and conjugated equine estrogens plus medroxyprogesterone acetate on choline acetyltransferase and acetylcholinesterase activities within different regions of the brain in cynomologus monkeys. All treatments were administered for 2 years. None of the treatments produced significant increases in either choline acetyltransferase or acetylcholinesterase in any of eight brain regions analyzed. In contrast, treatment with conjugated equine estrogens plus medroxyprogesterone acetate, but not conjugated equine estrogens alone, produced significant reductions in both choline acetyltransferase and acetylcholinesterase in the medial septum/diagonal band of Broca compared with untreated controls. Treatment with tibolone also resulted in significant reductions in both choline acetyltransferase and acetylcholinesterase in the medial septum/diagonal band of Broca, and this effect was dose-related. These findings are the first to report the effects of long-term therapies used by postmenopausal women on cholinergic measures in the primate brain. The findings are consistent with recent reports in rats, and suggest that any positive effects of long-term estrogen or hormone replacement therapy on cognitive processes are probably not due to significant effects on choline acetyltransferase or acetylcholinesterase activities.
Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, 1004 Salk Hall, Pittsburgh, PA 15261, USA. gibbs@pitt.edu
R B
RB
Gibbs
D
D
Nelson
M S
MS
Anthony
T B
TB
Clarkson
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D005260:Female; D020249:Hormone Replacement Therapy / Q000706:statistics & numerical data*; D008252:Macaca fascicularis; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D009652:Norpregnenes / Q000494:pharmacology*; D010052:Ovariectomy / Q000706:statistics & numerical data
D004966:Estrogens, Conjugated (USP); D009652:Norpregnenes; D017258:Medroxyprogesterone Acetate; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; C027385:tibolone