Cell-type-specific expression of rat steroid 5 alpha-reductase isozymes.

Abstract

The enzyme steroid 5a-reductase (EC 1.3.99.5) is a component of an intercellular signaling pathway that determines cell fate in the primordium of the mammalian reproductive tract. During male phenotypic sexual differentiation, the dihydrotestosterone product of this enzyme binds to the androgen receptor and initiates development of the external genitalia and prostate. Genes encoding two isozymes of steroid 5a-reductase with different biochemical properties and tissue distributions have recently been isolated. In the current study, we utilize in situ hybridization analysis to determine cell-typespecific expression patterns of the 5az-reductase isozyme mRNAs in two androgen target tissues (regenerating ventral prostate and epididymis) and a peripheral tissue (liver). In regenerating ventral prostate, the type 1 mRNA is expressed in basal epithelial cells whereas expression of the type 2 mRNA is largely confined to stromal cells. These results were confirmed by immunohistochemical analysis and are consistent with distinct roles played by the isozymes in the prostate. In the epididymis, both 5a-reductase isozyme mRNAs are expressed in epithelial cells. Only the type 1 mRNA is present in the liver.This mRNA is distributed in a striking spatial gradient extending from hepatocytes surrounding the portal triad (high expression) to those surrounding the central vein (low to absent expression). These findings demonstrate cell-type-specific expression of the steroid 5a-reductase isozymes and underscore their distinct and overlapping functions in androgen physiology.

Equine 5α-reductase activity and expression in epididymis

“…Although there is a preponderance of type 2 expression in primate epididymis (Mahony et al 1997(Mahony et al , 1998, both isozymes are still present, and men with a deficiency of the type 2 enzyme develop epididymis (Thigpen et al 1992). Similarly, both isozymes are expressed in rat epididymis (Berman & Russell 1993, Viger & Robaire 1996. Further studies investigating isozyme expression of 5α-reductases in other accessory sex glands are necessary to determine the patterns and relative levels in the male reproductive tract of the horse.…”

The localisation and expression of 5 alpha-reductase types I and II mRNAs in human hyperplastic prostate and in prostate primary cultures

“…Reports as to the cellular location of 5 R are also controversial: in rat, 5 R-I is in basal epithelial cells and the 5 R-II in stroma (Berman & Russell 1993). Silver et al (1994) have reported that human 5 R-II in some BPH specimens is predominantly in the basal epithelial cells whereas in other specimens it is in both stroma and basal epithelial cells.…”

Expression and regulation of steroid 5α-reductase in the genital tubercle of the fetal rat

“…This cell type specificity is characteristic of multiple embryonic structures in the reproductive tract including the genital tubercle/ phallus (Figs. 1-5), urogenital sinus, prostate, vagina, and bulbourethral gland (Berman et al, 1995), and the epididymis and prostate of the adult male animal (Berman and Russell, 1993). In the case of the genital tubercle, epithelia derived from both the ectoderm (e.g., cells of the surface epithelium, Fig.…”

“…The specificity of the 5a-reductase type 1 antibody is documented in Berman and Russell (1993). Exposure times for the in situ mRNA hybridization experiments ranged from 10 to 21 days.…”

“…These procedures were carried out as previously described (Berman and Russell, 1993;Berman et al, 1995) using 33 P radiolabeled probes to detect mRNAs and an avidin-biotin detection system with a diaminobenzidine tetrahydrochloride chromogenic substrate to detect 5a-reductase type 1 protein. The specificity of the 5a-reductase type 1 antibody is documented in Berman and Russell (1993).…”