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Ovarian steroid regulation of serotonin reuptake transporter (SERT) binding, distribution, and function in female macaques


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.

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We thank Dr D Hess of the Endocrine Services Core, ONPRC for the steroid hormone assays and Dr A Cornea of the Imaging and Morphology Core, ONPRC for assistance with the Confocal microscopy. Ms K Wolfrum at the Research Service, Veterans Affairs Medical Center, Portland, OR provided much appreciated technical support. Lundbeck, Copenhagen, Denmark, generously provided citalopram.

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Correspondence to C L Bethea.

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Supported by NIH grant MH62677 to CLB, U54 contraceptive Center Grant HD 18185 and RR000163 for the operation of ONPRC and Merit Review and Research Career Scientist Program from the Department of Veteran Affairs.

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Lu, N., Eshleman, A., Janowsky, A. et al. Ovarian steroid regulation of serotonin reuptake transporter (SERT) binding, distribution, and function in female macaques. Mol Psychiatry 8, 353–360 (2003).

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  • estrogen
  • progesterone
  • serotonin
  • primate
  • depression
  • hormone replacement therapy

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