Ovarian hormones influence the morphology, distribution, and density of tyrosine hydroxylase immunoreactive axons in the dorsolateral prefrontal cortex of adult rhesus monkeys.

The maturation, adult functioning and dysfunction of the prefrontal cortex in disorders such as schizophrenia show gender biases in human and non-human primates. Although the basis for the hormone influence suggested in these observations is unknown, one possibility is that circulating hormones stimulate catecholamine innervation in the frontal lobe. This innervation is essential for prefrontal cortical function, and gonadal, especially ovarian hormones, profoundly influence catecholamine function and physiology in subcortical structures. This study was undertaken to determine whether influence is also exerted upon the catecholamine innervation of the association cortex by combining ovarian hormone manipulation with immunocytochemistry for tyrosine hydroxylase in the dorsolateral prefrontal cortex of adult female macaque monkeys. Qualitative and quantitative analyses of immunoreactive fibers were carried out and compared in cortices of ovariectomized animals, ovariectomized animals treated with estrogen, ovariectomized animals treated with estrogen followed by progesterone, and in intact, age- and sex-matched controls. These analyses revealed striking, layer-specific anomalies in fiber morphology and profound reductions in fiber density in ovariectomized animals. While hormone replacement with estrogen alone had limited influence, estrogen followed by progesterone was particularly effective in restoring tyrosine hydroxylase innervation in ovariectomized animals. Thus, ovarian hormones appear to be potent regulators of the catecholamine innervation of the primate prefrontal cortex. Such regulation is anticipated in the gender differences observed in prefrontal cortical development and function, and may also be relevant for the prefrontal dysfunction in disorders such as schizophrenia.