Ovarian steroid regulation of monoamine oxidase-A and -B mRNAs in the macaque dorsal raphe and hypothalamic nuclei.
BACKGROUND
The serotonin neural system plays a pivotal role in mood, affective regulation and integrative cognition, as well as numerous autonomic functions. We have shown that ovarian steroids alter the expression of several genes in the dorsal raphe of macaques, which may increase serotonin synthesis and decrease serotonin autoinhibition. Another control point in aminergic neurotransmission involves degradation by MAO. This enzyme occurs in two isoforms, A and B, which have different substrate preferences.


OBJECTIVE
We questioned the effect of ovarian steroid hormones on MAO-A and MAO-B mRNA expression in the dorsal raphe nucleus and hypothalamus using in situ hybridization in non-human primates.


METHODS
Rhesus monkeys ( Macaca mulatta; n=5/group) were spayed and either placebo treated (controls), estrogen (E) treated (28 days), progesterone (P) treated (14 days placebo+14 days P), or E+P treated (14 days E+14 days E+P). Perfusion-fixed sections (25 microm) were hybridized with a 233 bp MAO-A, or a 373 bp MAO-B, radiolabeled-antisense monkey specific probes. Autoradiographic films were analyzed by densitometry, which was performed with NIH Image Software.


RESULTS
MAO-A and -B mRNAs were detected in the dorsal raphe nucleus (DRN) and in the hypothalamic suprachiasmatic nucleus (SCN), preoptic area (POA), paraventricular nucleus (PVN), supraoptic nucleus (SON), lateral hypothalamus (LH) and ventromedial nucleus (VMN). MAO-A mRNA optical density was significantly decreased by E, P, and E+P in the DRN and in the hypothalamic PVN, LH and VMN. Ovarian hormones had no effect on MAO-B mRNA expression in the DRN. However, there was a significant decrease in MAO-B optical density in the hypothalamic POA, LH and VMN with E, P or E+P treatment. Pixel area generally reflected optical density.


CONCLUSIONS
Ovarian steroids decreased MAO-A, but not B, in the raphe nucleus. However, both MAO-A and B were decreased in discrete hypothalamic nuclei by hormone replacement. These data suggest that the transcriptional regulation of MAO by ovarian steroids may play a role in serotonin or catecholamine neurotransmission and hence, mood, affect or cognition in humans.
Gundlah
Chrisana
C
Division of Reproductive Services, Oregon Regional Primate Research Center, Beaverton, OR 97006, USA.
Lu
Nick Z
NZ
Bethea
Cynthia L
CL
D000818:Animals; D001483:Base Sequence / Q000235:genetics; D004338:Drug Combinations; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology*; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D008995:Monoamine Oxidase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D011903:Raphe Nuclei / Q000187:drug effects / Q000201:enzymology*; D013256:Steroids
D004338:Drug Combinations; D004967:Estrogens; D012333:RNA, Messenger; D013256:Steroids; D011374:Progesterone; D008995:Monoamine Oxidase