DIFFERENTIAL-EFFECTS OF AROMATASE INHIBITION ON LUTEINIZING-HORMONE SECRETION IN INTACT AND CASTRATED MALE CYNOMOLGUS MACAQUES

To understand the role of central aromatization in feedback regulation of LH in nonhuman primates, we treated adult male cynomolgus monkeys with the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD). W e measured LH, testosterone (T), and ATD in systemic sera of blood sam ples drawn on a diurnal schedule (0900 and 2100 h). Each animal was bl ed for 4 pretreatment days from a femoral catheter after which they we re divided into the following treatment groups: castrated (Cx), n = 2; Cx + T, n = 6; Cx + T + ATD, n = 6; Cx + ATD, n = 3; and sham operate d + ATD, n = 3. Silastic capsules or packets containing T or ATD, resp ectively, were placed sc between the scapulae at the time of Cx or sha m treatment. In T-treated animals, T (20 mu g/kg body weight) dissolve d in propylene glycol was injected im at 2100 h to mimic the diurnal r ise of T observed in nonhuman primates. Animals were bled for 2 weeks after which they were killed, and selected brain areas were analyzed f or aromatase activity and cytosolic and nuclear androgen receptors. An imals treated with ATD had significantly reduced levels of aromatase a ctivity in selected regions of the hypothalamus, preoptic area, and th e amygdala (P < 0.05). Even though ATD inhibited brain aromatase activ ity, it did not prevent the negative feedback actions of T on LH secre tion after Cx. In addition, ATD by itself inhibited LH secretion after Cx and activated brain androgen receptors. These latter effects of AT D seemed to have been mediated through a metabolite. In sham-operated intact males, ATD produced variable surges of LH that were accompanied by elevations of T in the systemic circulation. These differential ef fects of ATD in intact vs. castrated animals demonstrate the importanc e of selecting the proper model system to study LH control mechanisms. In the intact animal, aromatization seems to play a role in regulatin g LH secretion, but the postcastration rise of LH seems to be regulate d differently.