title: Lack of ovarian steroid hormone regulation of norepinephrine transporter mRNA expression in the non-human primate locus coeruleus.
abstract: Decreases in ovarian steroids can negatively affect mood, and drugs which block the norepinephrine transporter (NET) or the serotonin transporter (SERT) alleviate depression. However, the respective contribution of the noradrenergic and serotonergic systems may vary depending upon the etiology of the depression. We previously demonstrated that E and P alter gene expression for tryptophan hydroxylase (TPH) and for the serotonin reuptake transporter (SERT) in raphe neurons of the rhesus monkey. In this study, we questioned whether the noradrenergic system contributes to depression related to the reproductive function in women, using a non-human primate model of the menstrual cycle. The effect of estrogen (E) or E plus progesterone (P) on the expression of the NET gene in the locus coeruleus (LC) was examined with in situ hybridization for NET mRNA. In addition, we questioned whether the neurons of the LC contain nuclear E or P receptors (ER/PR). Hence, immunocytochemistry for ER and PR were performed on adjacent sections. Treatment groups consisted of monkeys (n = 4 per treatment) which were ovariectomized/hysterectomized (spayed), E-treated (28 days) and E+P-treated (14 days E, +14 days E+P). Expression of mRNA for NET was unchanged at any level of the LC due to steroid treatment (p > .05). Neither ER nor PR were detected in the LC of any treatment group. Therefore, E and P in a treatment paradigm which mimics the menstrual cycle do not directly regulate NET mRNA expression in the non-human primate LC. In addition, the noradrenergic neurons of the primate LC lack nuclear receptors for ovarian steroids. These data suggest that the noradrenergic system may not contribute significantly to depression related to changes in ovarian hormones.
authors.affiliation: Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton 97006, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: Schutzer
authors.forename: C L
authors.initials: CL
authors.lastname: Bethea
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D008125:Locus Coeruleus / Q000378:metabolism*; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010053:Ovary / Q000502:physiology*; D011374:Progesterone / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters
chemical_list: D002352:Carrier Proteins; D004967:Estrogens; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters; D011374:Progesterone