ANDROGENS TRANSCRIPTIONALLY REGULATE THE EXPRESSION OF CYSTATIN-RELATED PROTEIN AND THE C3 COMPONENT OF PROSTATIC BINDING-PROTEIN IN RAT VENTRAL PROSTATE AND LACRIMAL GLAND

In this report, it is demonstrated that the C3 component of prostatic binding protein (PBP) is also expressed and androgen regulated in the exorbital lacrimal gland, as shown previously for cystatin-related pro tein (CRP), another abundant secretory protein from the ventral prosta te. The presence of C3 messenger RNA (mRNA) could be demonstrated by b oth Northern blot hybridization and,PCR amplification and sequencing. The mRNAs encoding the C1 and C2 components of PBP, however, were unde tectable. At the protein level, the C3 component in the lacrimal gland is glycosylated and linked by disulfide bridges to a new 10-kDa compo nent not reacting with the PBP antiserum. As shown previously for CRP, the expression of C3 in the lacrimal gland requires the simultaneous presence of androgens and a functional androgen receptor. The effects of castration and androgen treatment on CRP and C3 mRNA concentrations were studled by Northern blot and dot blot hybridization; effects on transcription rates were determined by nuclear run-on assay. Two days after castration, the relative abundance of CRP mRNA had declined sign ificantly (P < 0.01) to 10.5 +/- 1.5% (+/-SEM) of precastration levels in the prostate and to 14.5 +/- 8.0% in the lacrimal gland; the trans cription rates declined to 14.3% and 10.0%, respectively. The C3 mRNA level and transcription rate in the prostate showed a more moderate de crease (P < 0.05) to 40.6 +/- 8.5% and 41.7%, but were hardly measurab le in the lacrimal gland. Androgen administration resulted in a rapid increase in the transcription rates, which reached or exceeded control levels after 6-9 h of treatment and clearly preceded the increase in mRNA levels. It is concluded that the lacrimal gland, which can be stu died conveniently in female and long term androgen-depleted animals of fers a suitable model for the study of androgen-regulated gene express ion.