Transcription of prostatic steroid binding protein (PSBP) gene is induced by epithelial–mesenchymal interaction
Authors: Takeda Hiroyuki , Suematsu Naoya , Mizuno Takeo 
Published: April 2021

The prostate gland develops from the fetal urogenital sinus at the base of the urinary bladder. It finally differentiates into three lobes; ventral, lateral and dorsal lobes of the prostate. In spite of their common developmental origin and similar glandular structure, these lobes show the different biochemical characteristics, for example, in the proteins they secrete. In the present study, we investigate the involvement of the epithelial–mesenchymal interaction in the lobe-specific differentiation of the prostatic epithelium by means of epithelial–mesenchymal recombination experiments. We have used a prostatic steroid-binding protein (PSBP) as a specific differentiation marker for the ventral prostate. PSBP is a tetramer which consists of 2 subunits, one containing the polypeptides Cl and C3 and the other containing the polypeptides C2 and C3. Northern analysis with a complementary DNA probe encoding Cl peptide (PSBP-C1) revealed that the mRNAs were detected exclusively in the ventral prostate but not in the dorsal prostate or in other organs such as urinary bladder and kidney. In situ hybridization with a complementary (anti-sense) RNA probe demonstrated that the transcripts were found only in the epithelium, not in the mesenchyme of the ventral prostate. In situ hybridization also showed that, in normal development, the mRNAs for PSBP-C1 in the ventral epithelium were first detectable at day 14 after birth, coinciding with the onset of its cytodifferentiation, and that they reached mature levels by day 21.

We then carried out tissue-recombination experiments to examine whether the transcription of the PSBP-C1 gene in the epithelium is affected by the surrounding mesenchyme. Fetal urogenital sinuses were subdivided into ventral and dorsal halves. Following collagenase treatment, both halves were separated into their epithelial and mesenchymal compartments. Homotypic (ventral epithelium plus ventral mesenchyme [Ev/ Mv] and dorsal epithelium plus dorsal mesenchyme [Ed/Md]) and heterotypic (ventral epithelium plus dorsal mesenchyme [Ev/Md] and dorsal epithelium plus ventral mesenchyme [Ed/Mv]) recombinations were carried out. After 4–5 weeks of growth in male host, the glandular structures characteristic for prostate glands were formed in all explants. However, in situ hybridization revealed the transcripts of the PSBP-C1 gene only in the epithelium associated with the ventral mesenchyme (Ev/Mv and Ed/Mv). In contrast, the transcripts were never found in the epithelium associated with the dorsal mesenchyme (Ev/Md and Ed/Md). Moreover, we found that the urinary bladder epithelium has limited ability to transcribe the PSBP-C1 gene under the influence of the ventral mesenchyme of the urogenital sinus.

These results indicate that the ventral mesenchyme is a potent inducer for ventral prostate-specific cytodifferentiation and suggest that the lobe-specific differentiation in the prostatic epithelium could be directed by its surrounding mesenchyme through epithelial–mesenchymal interactions.