HE2 beta and HE2 gamma, new members of an epididymis-specific family of androgen-regulated proteins in the human

HE2 is an epididymis-specific sperm-binding secretory protein. We isolated a family of HE2-related complementary DNAs from a human caput/corpus librar y. The transcripts code for identical 71-amino acid N-termini and different C-termini, and 5'- and 3'-untranslated regions. Compared with the original HE2, HE2 beta and HE2 gamma proteins have a 25-amino acid deletion near th e C-terminus, and HE2 gamma isoforms have a second deletion. These frame-sh ifting deletions result in C-termini differing in length, amino acid sequen ce, including number of cysteines, and isoelectric point. Identical sequenc es and deletion start and stop points indicate the HE2 isoforms are derived from alternative splicing of 8 or more exons of a single gene. Northern hy bridization revealed that the 0.9-kb messenger RNA (mRNA) is most abundant in human caput; there is much less of it (20%) in corpus and little (<5%) i n cauda. In castrated Macaca mulatta, HE2 mRNA decreased to 10% of sham-ope rated levels. Testosterone replacement maintained HE2 mRNA 3- to B-fold hig her than castrate levels, indicating its androgen dependence. Immunohistoch emical staining revealed that the beta 1 form is highly expressed in princi pal cells of the initial segment and caput. It is secreted into the lumen a nd binds to the sperm surface in the postacrosomal and neck regions. The be ta 2 form is expressed in principal cells primarily in efferent ducts.