title: Initiation of secretory activity of rat prostatic epithelium in organ culture.
abstract: Functional differentiation of prostatic epithelium is manifested by the production of tissue specific secretory proteins. In vivo production of these proteins is dependent on the presence of serum androgens. A serum-free organ culture system was used to examine the initiation of prostatic epithelial cytodifferentiation in vitro using two rat prostate specific secretory proteins (DP-1 and probasin) as markers of epithelial cytodifferentiation. The dorsal-lateral and anterior prostatic (AP) lobes from 12-day-old rats were cultured for 6 days in serum-free medium in the presence or absence of androgens. At the start of culture, secretory proteins DP-1 and probasin were undetectable using Western blot analysis. DP-1 and probasin were produced by explants cultured in the presence of androgens but were not detected in the absence of androgens. Dose-response studies were carried out for testosterone (T), 5 alpha-dihydrotestosterone (DHT), 5 alpha-Androstan-3 alpha, 17 beta-diol (3 alpha-Adiol), and two synthetic androgens: 17 alpha-methyl-19-nortestosterone (MENT) and methyltrienolone (R1881). All androgens used were capable of inducing expression of DP-1 and probasin in vitro. T, R1881, and Ment were effective at doses of 10(-7) M to 10(-9) M, whereas both DHT and 3 alpha-Adiol were able to induce DP-1 and probasin at concentrations as low as 10(-10) M. Estrogen (17 beta-Estradiol), hydrocortisone (11 beta, 17 alpha, 21-trihydroxypregn-4-ene-3, 20-dione), and progesterone (4-pregnen-3, 20-Dione) were ineffective in inducing prostatic secretory activity. Hydroxyflutamide (alpha-alpha-alpha-trifluro-2-methyl-4'-nitro-m-lactoluidide ) blocked the induction of secretory activity elicited by T. From histological sections, it was observed that explants cultured with T exhibited tall columnar epithelial morphology with organized stromal components. Tissue sections of explants cultured without T exhibited a cuboidal to low columnar morphology with less organized stromal components when compared with glands cultured with T. A DNA synthetic index was established to measure proliferation in the explants at the end of the culture period. Explants cultured in the presence of T exhibited greater DNA synthetic activity than explants cultured in the absence of T (P < 0.05). Using this serum-free model, we can explore the mechanism for the initiation of secretory cytodifferentiation.
authors.affiliation: Anatomy Department, University of California, San Francisco 94143-0452, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Lopes
authors.forename: B A
authors.initials: BA
authors.lastname: Foster
authors.forename: A A
authors.initials: AA
authors.lastname: Donjacour
authors.forename: G R
authors.initials: GR
authors.lastname: Cunha
mesh_terms: D000727:Androgen-Binding Protein / Q000378:metabolism; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D004247:DNA / Q000096:biosynthesis; D004848:Epithelium / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009924:Organ Culture Techniques; D011467:Prostate / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013739:Testosterone / Q000494:pharmacology
chemical_list: D000727:Androgen-Binding Protein; D000728:Androgens; C027519:probasin; D013739:Testosterone; D004247:DNA