Quantitative assessment of the biological effects of follicle regulatory protein on dihydrotestosterone-maintained spermatogenesis in hypophysectomized rat

Follicle regulatory protein (FRP) isolated from porcine ovarian follicles influences folliculogenesis through a paracrine mechanism. A similar protein has been found in the testes and seems to have some inhibitory effects on spermatogenesis when administered to intact male experimental animals. On the basis of female and male studies, it has been ascertained that the effects of FRP are at the level of gonads and not the pituitary or the hypothalamus. In the studies with intact males it was not possible to determine the exact site of FRP action on the testes. Dihydrotestosterone (DHT) has been shown to maintain spermatogenesis in hypophysectomized rats. In order to determine if the inhibitory effects of FRP are at steps prior to the formation of DHT, FRP was administered to hypophysectomized rats that were injected with DHT. Groups of adult rats were hypophysectomized and treated daily with FRP, DHT, FRP + DHT, or vehicle alone for 30 days. At necropsy, body, testes, prostate glands, and seminal vesicle weights were recorded. One testis and sexual accessory glands were fixed for histological evaluation. The contralateral testis was decapsulated, six 2 mm segments of seminiferous tubules, representing defined stages of spermatogenesis, were isolated by transillumination-assisted microdissection, and spermatogenic cells were quantified by DNA flow cytometry. Histologically, the seminiferous tubules of vehicle-treated hypophysectomized controls showed advanced regression. Rats treated with FRP alone showed similar degeneration. On the other hand, rats treated with DHT showed maintenance of spermatogenesis comparable to normal controls. The testes of rats treated with FRP + DHT were indistinguishable from those treated with DHT only. Flow cytometric quantification of germinal cells from all groups confirmed the histological findings. In this study FRP did not exert deleterious effects on DHT-maintained spermatogenesis. This finding suggests that the inhibitory effects of FRP on spermatogenesis in intact animals may not be a direct effect on spermatogenic cells but may impair androgen action or production or DHT formation.