Gonadectomy and hormone replacement exert region- and enzyme isoform-specific effects on monoamine oxidase and catechol-O-methyltransferase activity in prefrontal cortex and neostriatum of adult male rats

Abstract

Sex differences and gonadal hormone influences are well known for diverse aspects of forebrain amine and indolamine neurotransmitter systems, the cognitive and affective functions they govern and their malfunction in mental illness. This study explored whether hormone regulation/ dysregulation of these systems could be related to gonadal steroid effects on catechol-Omethyltransferase and monoamine oxidase which are principal enzymatic controllers of forebrain dopamine, serotonin and norepinephrine levels. Driven by male over female differences in cortical enzyme activities, by male-specific associations between monoamine oxidase and catechol-Omethyltransferase gene polymorphisms and cognitive and dysfunction in disease and by malespecific consequences of gene knockouts in mice, the question of hormone sensitivity was addressed here using a male rat model where prefrontal dopamine levels and related behaviors are also known to be affected. Specifically, quantitative O-methylation and oxidative deamination assays were used to compare the activities of catechol-O-methyltransferase's soluble and membrane-bound isoforms and of monoamine oxidase's A and B isoforms in the pregenual medial prefrontal cortex and dorsal striatum of male rats that were sham operated, gonadectomized or gonadectomized and supplemented with testosterone propionate or with estradiol for 28 days. These studies revealed significant effects of hormone replacement but not gonadectomy on the soluble but not the membrane-bound isorfom of catechol-O-methyltransferase in both striatum and cortex. A significant, cortex-specific testosterone-but not estradiol-attenuated effect (increase) of gonadectomy on monoamine oxidase's A but not B isoform was also observed. Although none of these actions suggest potential roles in the reguation/dysregulation of prefrontal dopamine, the suppressive effects of testosterone on cortical monoamine oxidase-A that were observed could have bearing on the increased incidence of cognitive deficits and symptoms of depression and anxiety that are repeatedly observed in males in conditions of hypogonadalism related to aging, other biological factors or in prostate cancer where androgen deprivation is used as a neoadjuvant treatment. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2011 February 3. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe prefrontal cortices are essential in mediating highest order executive functions such as planning, working memory and behavi...

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