TY - JOUR
T1 - Ovarian steroid regulation of serotonin reuptake transporter (SERT) binding, distribution, and function in female macaques
AU - Lu, N. Z.
AU - Eshleman, A. J.
AU - Janowsky, A.
AU - Bethea, C. L.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003
Y1 - 2003
N2 - The serotonin reuptake transporter (SERT) plays an important role in serotonin neurotransmission and in several psychopathological disorders such as depression and anxiety disorders. In this study, we investigated whether the ovarian steroids, estrogen (E) and progesterone (P) regulate SERT binding, intracellular distribution, and function using [3H]citalopram ligand binding with quantitative autoradiography, immunofluorescence histochemistry with confocal microscopy and [3H]serotonin uptake, respectively. Ovariectomized macaques received either placebo, E alone, P alone or E plus P for 28 days. In the raphe, E, P, and E+P treatments did not change SERT binding density. In several hypothalamic nuclei, [3H]citalopram binding was increased by E, P, and E+P. Immunofluorescent SERT in serotonin soma was intracellular and similar among treatments. In the hypothalamus, immunofluorescent SERT was located along the serotonergic axons and there was a significant proliferation of immunofluorescent fibers in hormone-treated animals. In addition, E and E+P treatment increased serotonin uptake in the basal ganglia. These findings suggest that ovarian hormones regulate SERT protein expression and distribution, perhaps via extracellular serotonin or mRNA stability, but not solely at the level of gene transcription. Further investigation on the possible action of ovarian steroids on the directionality of SERT transport is indicated.
AB - The serotonin reuptake transporter (SERT) plays an important role in serotonin neurotransmission and in several psychopathological disorders such as depression and anxiety disorders. In this study, we investigated whether the ovarian steroids, estrogen (E) and progesterone (P) regulate SERT binding, intracellular distribution, and function using [3H]citalopram ligand binding with quantitative autoradiography, immunofluorescence histochemistry with confocal microscopy and [3H]serotonin uptake, respectively. Ovariectomized macaques received either placebo, E alone, P alone or E plus P for 28 days. In the raphe, E, P, and E+P treatments did not change SERT binding density. In several hypothalamic nuclei, [3H]citalopram binding was increased by E, P, and E+P. Immunofluorescent SERT in serotonin soma was intracellular and similar among treatments. In the hypothalamus, immunofluorescent SERT was located along the serotonergic axons and there was a significant proliferation of immunofluorescent fibers in hormone-treated animals. In addition, E and E+P treatment increased serotonin uptake in the basal ganglia. These findings suggest that ovarian hormones regulate SERT protein expression and distribution, perhaps via extracellular serotonin or mRNA stability, but not solely at the level of gene transcription. Further investigation on the possible action of ovarian steroids on the directionality of SERT transport is indicated.
KW - Depression
KW - Estrogen
KW - Hormone replacement therapy
KW - Primate
KW - Progesterone
KW - Serotonin
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U2 - 10.1038/sj.mp.4001243
DO - 10.1038/sj.mp.4001243
M3 - Article
C2 - 12660809
AN - SCOPUS:0038143608
VL - 8
SP - 353
EP - 360
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
IS - 3
ER -