Effects of ovarian steroids and raloxifene on proteins that synthesize, transport, and degrade serotonin in the raphe region of macaques.
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 raloxifene 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 raloxifene 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.
Smith
Lisa J
LJ
Division of Reproductive Sciences, Oregon National Primate Research Center, Beaverton, OR, USA.
Henderson
Jessica A
JA
Abell
Creed W
CW
Bethea
Cynthia L
CL
D000818:Animals; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000096:biosynthesis* / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins
D004967:Estrogens; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D020849:Raloxifene Hydrochloride; D011374:Progesterone