The effect of flutamide on expression of androgen and estrogen receptors in the gubernaculum and surrounding structures during testicular descent

Abstract

Background/Purpose Inguinoscrotal testicular descent is controlled by androgens between embryonic days E16-19, but androgen receptor (AR) and estrogen receptor (ER) locations are unknown. We aimed to find AR, ER α, and ER β in the gubernaculum and inguinal fat pad (IFP) in normal rats and after flutamide treatment. Methods Sprague-Dawley timed-mated rats were injected with flutamide (75 mg/kg body weight/5% ethanol + oil) on E16-19 or vehicle alone. Male fetuses or pups (5-10/group) were collected at E16; E19; and postnatal (P) days 0, 2, 4, 8. Sections were prepared for hematoxylin and eosin or immunohistochemistry for AR, ERα, and ERβ. Receptor labeling was quantitated as distinct nuclear labeling/100 μm 2 in gubernaculum and IFP. Results There was minimal gubernacular AR-labeling until E19, dramatically increasing postnatally. By contrast, at E16-E19 there was significant IFP AR immunoreactivity suppressed by flutamide ( P < .05). No ERα expression was observed, but ERβ was expressed in both gubernaculum and IFP, maximally at E16, but unchanged by flutamide. Conclusions During the androgen sensitivity window (E16-19), the gubernaculum contains ERβ but minimal ERα or AR, while the IFP, which is supplied by the genitofemoral nerve, contains abundant AR that are flutamide-sensitive. These results suggest that the IFP could be the site of androgenic action controlling gubernacular development.