59 Secretory Lipophilins: A Tale of Two Species ROBERT I. LEHRER, a,b,c TUNG NGUYEN, b CHENGQUAN ZHAO, b CHEN XIAN HA, b AND BEN J. GLASGOW d,e b Department of Medicine, c Molecular Biology Institute, d Department of Pathology, and e Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, California 90095, USA ABSTRACT: Secretory lipophilins are “lipid-loving” proteins that are major constituents of several mammalian secretions, including the prostatic fluid of rats and the tears of humans and rabbits. These proteins form covalent hetero- dimers that are stabilized by three intramolecular cystine disulfide bonds. The heterodimers, some of which are glycosylated, may undergo additional non- covalent assembly to form tetramers. The peptide components found in secre- tory lipophilins are from two subfamilies: lipophilins A/B and lipophilin C. The C subfamily members described in this report are three rabbit and one human lipophilin, plus human mammaglobin and the C3 subunit of rat prostatein. Hu- man A/B and C lipophilins are expressed by many tissues and are especially prominent in endocrine-responsive organs. The gene for human lipophilin B resides at chromosome 10q22-23. This region harbors the PTEN/MMAC1 gene and is believed to contain additional tumor suppressor genes. Although the functions of secretory lipophilins are imperfectly understood, their abundance in glandular secretions and in hormone-responsive tissues suggests that they deserve considerably more attention than they have received to date. INTRODUCTION Secretory lipophilin is a nonglycosylated, heterodimeric protein that occurs in human tears at concentrations above 100 μg/mL. 1,2 It has two subunits, components A and C, that are connected by three intermolecular cystine disulfide bonds. We dis- covered it by accident while mapping the peptides of human tears during a search for antimicrobial molecules. Although secretory lipophilins had unimpressive anti- microbial properties, we obtained N-terminal sequence data to identify this unfamil- iar molecule. When it proved to be a novel homologue of rat prostatein, the major secretory product of the ventral prostate, it caught our eye and has remained there since. Rat prostatein has received several alternative names, including “prostatic bind- ing protein”, “prostatic α-protein”, “estramustine binding protein” (estramustine is an antineoplastic agent that contains estradiol linked to nornitrogen mustard), “pros- tatic secretion protein”, and “prostatic steroid-binding protein”. 3–6 For simplicity, a Address for correspondence: Robert I. Lehrer, Department of Medicine, CHS 37-062, UCLA Center for the Health Sciences, 10833 LeConte Avenue, Los Angeles, CA 90095-1690. Voice: 310-825-5340; fax: 310-206-8766. rlehrer@mednet.ucla.edu