A PUTATIVE 5-ALPHA-REDUCTASE INHIBITOR DEMASCULINIZES PORTIONS OF THEZEBRA FINCH SONG SYSTEM

One model of the sexual differentiation of the zebra finch song system holds that both major metabolites of testosterone, dihydrotestosteron e (DHT) and estradiol(E(2)), act together to masculinize the song syst em. To test this model, we administered a putative inhibitor of 5 alph a-reductase (MK-434) to decrease the synthesis of DHT from testosteron e (T) in hatchling zebra finches. We tested MK-434's inhibition of 5 a lpha-reductase, 5 beta-reductase, and aromatase in vivo and in vitro. In vivo, MK-434 significantly inhibited 5 alpha-reductase activity but also reduced the activities of SP-reductase and aromatase. In vitro, MK-434 was extremely effective in inhibiting 5 alpha-reductase in the rat prostate but only slightly inhibited 5 alpha-reductase in the zebr a finch telencephalon, where it also reduced aromatase and 5 beta-redu ctase activities. These results suggest that MK-434 might differential ly influence the availability of androgenic and estrogenic substrates, depending on the relative abundance of these enzymes in brain. lMK-43 4 demasculinized (decreased) the number and decreased the density of R A neurons but did not significantly affect any other sexually dimorphi c aspect of the song system, including the volumes of RA, HVC, and Are a X; the size of neural somata in lMAN, HVC, and RA; and the number of neurons in HVC and lMAN. The differential influence of MK-434 on sexu ally dimorphic characteristics suggests that the various sexually dimo rphic characteristics of the song system (1) are sensitive to differen t hormones, depending on the characteristic; or (2) have different sen sitivities to hormone levels, some being easily affected by slightly r educed hormone levels whereas others are not; or (3) have markedly dif ferent critical periods depending on the characteristic. Regardless of the reason(s) for differential effects on the sexually dimorphic char acteristics of the song system, the data clearly suggest that steroid hormones play a role in the normal masculine development of the song s ystem.