Estrogen and Castration-Induced Effects on Canine Prostatic Fine Structure and Ci9-steroid Metabolism

Abstract

Canine prostate tissue taken from the same gland before and 30 days after administration of estradiol-17β cyclopentanepropionate (ECP) or orchiectomy was examined by light and electron microscopy and incubated with 14C-labeled testosterone, 4-androstene-3,17-dione (androstenedione) and 17β-hydroxy-5α-androstan- 3-one (5α-dihydrotestosterone) with and without cofactor supplementation. Whereas gonadectomy caused atrophy of prostatic epithelium, the dose schedule of ECP induced squamous metaplasia. These histological markers were characteristic end-points of the experimental procedures. Cellular changes were less specific when studied by electron microscopy. ECP treatment and castration gave rise to similar nuclear and cytoplasmic alterations in glandular epithelium, notably change from nuclear euchromatin to heterochromatin patterns. Only the presence of numerous lysosomes and more severe effects on granular endoplasmic reticulum served to distinguish the prostatic fine structure of castrates from that of ECP-treated dogs. Testosterone transformation by minced biopsy tissue was predominantly reductive, with formation of the “active androgens,” 5α-dihydrotestosterone, 5αandrostane- 3β,17β-diol and 5α-androstane-3α, 17β-diol, as the principal identified metabolites. ECP treatment caused substantial increase of substrate transformation over levels found in biopsy specimens and a shift from reductive to oxidative metabolism, with preponderant conversion to the weak androgen, androstenedione. The shift to androstenedione formation also occurred in the gland of the castrate, but the extent of testosterone metabolism did not change appreciably from the pre-ablative level and reduction of 5α-dihydrotestosterone substrate to the 5α-androstanediols remained substantial. The changes in prostatic Ci9-steroid metabolism may be explained by direct estrogen inhibition, and castration-mediated lysosomal digestion, of microsomal Δ4-3-keto-C19-steroid 5α-reductase, with concomitant release of unaffected microsomal 17β-hydroxy-C19-steroid oxidoreductase into the cytosol. The relative contributions of the reductive and oxidative pathways of prostatic C19-steroid metabolism may reflect the androgenestrogen balance of the endocrine milieu to which the gland is exposed. (Endocrinology89: 465, 1971)