Distribution of estradiol‐17β hydroxysteroid oxidoreductase in the urogenital tract of control and neonatally estrogenized male mice: Immunohistochemical, enzymehistochemical, and biochemical study

Abstract

The present study was conducted to investigate the regional distribution of the enzymes catalyzing the interconversion of the hydroxyl and carbonyl groups at C-17 of the estrogen molecule within the male urogenital tract of adult mouse and to test the hypothesis, whether regional differences in the distribution are critical for estrogen responses. The highest ratios of NADPH-dependent 3H-estrogen reduction to oxidation at C-17 of cell-free homogenates were obtained from coagulating gland and seminal vesicle as well as from the prostatic and lower intrapelvic urethra, which are considered the most estrogen-sensitive parts of the male urogenital tract. Both NADP- and NAD-dependent oxidation of 3H-17 beta-estradiol were low or nondetectable at these sites. The epithelium of the lower and prostatic urethra as well as the periurethral collecting ducts were stained with the antibody prepared against human placental 17 beta-hydroxysteroid oxidoreductase. The NAD-dependent 3H-estradiol-17 beta oxidase activity was highest in the bladder epithelium, and the activity declined sharply in the urinary tract from the bladder downward. The lowest detectable activities were found in vas deferens and prostate (combined ventral and dorsolateral lobes). The uneven distribution of estradiol-17 beta oxidase activity may provide additional explanation for the regional differences of estrogen responses. The NADPH-dependent 17 beta-reduction of estrone and the immunohistochemical staining of the human placental estradiol-17 beta oxidoreductase antigenicity were not significantly altered after neonatal estrogenization. These findings do not lend any support to the idea that the increased estrogen sensitivity observed after neonatal estrogenization is associated with changes in 17 beta-oxidoreduction. However, the possibility remains that there are specific sites (e.g., epithelium of prostatic urethra and collecting ducts) in which the changes in 17 beta-oxidoreduction of estrogen does play a role in the regulation of estrogen action.

Estrogen-Specific 17 -Hydroxysteroid Oxidoreductase Type 1 (E.C. 1.1.1.62) as a Possible Target for the Action of Phytoestrogens

“…For in-line detection of radioactive metabolites, the eluent of the HPLC column was continuously mixed with liquid scintillant and then monitored with an in-line radioactivity detector. Details of separation and quantification of [3H]labeled steroids have been described previously (30). Reductase activities were calculated as percentages of [3H]estrone converted to [3H]estradiol.…”

“…1.1.1.62, also known as l7P-hydroxysteroid dehydrogenase Type 1 or 17P-HSD Type 1). This enzyme is expressed in both steroidogenic cells, such as ovarian granulosa cells (24,25) and placental trophoblasts (26), as well as in some target tissues of estrogen action, such as normal and malignant breast and endometrium (27)(28)(29) and in the epithelium of the prostatic urethra and prostatic collecting ducts adjacent to estrogen receptor positive stroma (30). If such inhibition were present, it would lead to a decreased estrogen effect by interfering with estradiol biosynthesis at the ovarian and target cell level.…”

Developmental estrogenization and prostatic neoplasia

“…Similar localization of the estrogen-specific 17P-hydroxysteroid oxidoreductase provides further evidence for the homology. The epithelium of the urethra in the region of the seminal colliculus and prostatic collecting ducts is strongly positive for this enzyme in both mouse and human prostate [128,129]. The antibody, which was prepared against the enzyme protein purified from the human placenta, also stains the metaplastic epithelium seen in the estrogen-treated mouse.…”

The mouse as a model to investigate sex steroid metabolism in the normal and pathological prostate

“…However, the specific subtype(s) primarily responsible for enzymatic metabolism in the mouse prostate are yet to be definitely identified. Reductive 17␤HSD activity, measured by the conversion of radiolabeled androstenedione to T and without regard to subtype, has been observed in the mouse prostate [149] and varies between lobes and according to age in the rat [168] and mouse [169]. The candidates capable of producing active androgens are types 1, 3 and 5 based on their known activities for conversion of androstenedione to T.…”