期刊
NEUROPSYCHOPHARMACOLOGY
卷 29, 期 11, 页码 2035-2045出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.npp.1300510
关键词
serotonin; macaques; tryptophan hydroxylase; phosphorylation; monoamine oxidases; reuptake transporter; Western blots; estrogen; progesterone; raloxifene; selective estrogen receptor modulator; SERM
资金
- NCRR NIH HHS [RR000163] Funding Source: Medline
- NICHD NIH HHS [HD 18185] Funding Source: Medline
- NIMH NIH HHS [MH62677] Funding Source: Medline
- NINDS NIH HHS [NS24932] Funding Source: Medline
In the monkey dorsal raphe, we reported that 1-month (mo) of estrogen replacement, with or without progesterone supplementation for 14 days, significantly increased tryptophan hydroxylase-1 (TPH-1) mRNA; decreased serotonin reuptake transporter (SERT) mRNA and decreased monoamine oxidase (MAO)-A mRNA, but had no effect on MAO-B mRNA. Here, we questioned what effect would 1 or 5 mo of ovarian hormones or the selective estrogen receptor modulator (SERM), raloxifene, have on TPH protein and phosphorylation, and on protein expression of SERT, MAO-A or MAO-B? Raloxifene antagonizes estrogen in breast or uterus, but estrogen-like activities in the brain have been reported. Cytoplasmic and membrane extracts of the dorsal raphe region were processed for Western blotting. TPH, phosphoserine, SERT, MAO-A, and MAO-B were detected with specific antibodies. The optical densities of the signals were measured with NIH image and analyzed by ANOVA. Both 1 and 5 mo of estrogen, with or without progesterone, and 5 mo of raloxifene significantly increased TPH protein, Administration for 5 mo of estrogen plus progesterone and raloxifiene also increased TPH phosphorylation. Estrogen, with or without progesterone, for 1 mo had no effect on SERT protein. However, 5 mo of estrogen and 5 mo of raloxifiene increased SERT protein. Estrogen alone or combined with progesterone for 1 mo caused a significant reduction in MAO-A. Yet, after 5 mo of the same treatments, MAO-A was not different from spayed controls. Estrogen alone had no effect on MAO-B. However, the addition of progesterone significantly increased MAO-B. Raloxifene for 5 mo had no effect on MAO-A or MAO-B. Thus, to various extents, estrogen, progesterone, and raloxifene may increase serotonin production and transport. The expression of the degradative enzymes suggests a complex combination of gene transcription, post-transcriptional processing, and substrate feedback mechanisms.
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