Perinatal gonadectomy exerts regionally selective, lateralized effects on the density of axons immunoreactive for tyrosine hydroxylase in the cerebral cortex of adult male rats.

The catecholamine innervation of the cerebral cortex is essential for its normal operations and is implicated in cortical dysfunction in mental illness. Previous studies in rats have shown that the maturational tempo of these afferents is highly responsive to changes in gonadal hormones. The present findings show that perinatal hormone manipulation also has striking, region- and hemisphere-specific consequences for cortical catecholamines in adulthood. The effect of perinatal gonadectomy on catecholamines was examined in representative sensory, motor, and association cortices of adult male rats by combining hormone manipulation with immunocytochemistry for tyrosine hydroxylase, a rate-limiting enzyme in catecholamine biosynthesis. Qualitative and quantitative comparison of immunoreactivity in rats perinatally gonadectomized or sham-operated revealed complex changes in gonadectomized subjects; in cingulate cortex, TH immunoreactivity was strongly and bilaterally diminished, in sensory and motor cortices, axon density was decreased in left hemispheres, but was minimally affected on the right, and in a premotor cortex, gonadectomy was without significant effect in either hemisphere. Corresponding analyses in gonadectomized rats supplemented with testosterone revealed a protective influence, albeit one in which TH immunoreactivity so showed regional and hemispheric variability in responsiveness to hormone replacement. These complex patterns of TH sensitivity suggest highly asymmetric hormone stimulation of cortical catecholamines. Such discriminative action may contribute to sex differences in the functional maturation and lateralization of the cortex and may also have bearing on disorders such as dyslexia, which show sexual dimorphisms, and in which functional laterality of the cortex may be particularly at issue.