Evidence that brain aromatization regulates LH secretion in the male dog

A variety of data suggest an independent role for androgens and estrogens in the regulation of luteinizing hormone (LH) secretion in the male. Estrogens, in the male are primarily derived from testicular androgens that are aromatized both in peripheral tissues and in the CNS. Our prior data suggested a pharmacologic regimen that blocked CNS aromatization without lowering peripheral estrogen or testosterone levels. Such experimental conditions would permit assessment of the relative roles of CNS versus peripheral aromatization in the regulation of LH secretion. We utilized this regimen (aminoglutethimide, a potent aromatase inhibitor, and hydrocortisone) in seven adult male dogs for 14 days. Plasma LH rose to castrate levels, 450% above control values on days 7 and 14. These LH increments stimulated similar rises in androstenedione, testosterone, and dihydrotestosterone. In contrast, plasma estrone and estradiol concentrations remained constant. The induction of castrate LH levels without a concomitant fall in peripheral androgens or estrogens is best explained by a block of central aromatization and thus a reduction in local hypothalamic concentrations. We conclude that aromatization in the CNS rather than peripheral tissues is the more important site with respect to LH negative feedback in the male dog.