cDNA cloning and regulation of two sex-hormone-repressed hamster tear lipocalins having homology with odorant/pheromone-binding proteins

A major 20-kDa protein is female-specifically expressed in exorbital lacrimal gland (LG) of hamsters and secreted in tears. Here, we identify this female-specific LG protein (FLP) as a lipocalin, having 85% protein sequence identity with male-specific submandibular salivary gland proteins (MSP) secreted in saliva and urine of male hamsters. MSP is also female-specifically expressed in LG and secreted in tears but FLP was undetectable in submandibular gland (SMG). FLP and MSP have similar sex-hormonal regulation in LG, which is different from regulation of MSP in SMG. Female-specific expression of FLP and MSP in LG is due to their incomplete repression by endogenous estrogens and gonadectomy in both sexes and lactation in females resulted in their marked induction, which was prevented by estrogen or androgen treatment. FLP and MSP show best sequence identity with odorant/pheromone-binding lipocalins (58-29%). Maximum identity (58%) is with rat odorant-binding protein (OBP) expressed in lateral nasal glands, followed by aphrodisin of hamster vaginal discharge (39%). Cognate transcript and a cross-reacting 20-kDa protein were detected in nasal glands of rat in both sexes but not in hamsters. Results suggest that two closely related lipocalin genes encode FLP and MSP, which are evolutionarily closer to rat OBP than to hamster aphrodisin and these have evolved different tissue-specificity and sex-hormonal regulation. Possible functions for FLP and MSP are suggested, considering their homology to odorant/pheromone-binding lipocalins, their presence in tears, saliva and urine as well as their sex-specific and lactation-induced expression.