Structure, Evolution, and Expression of Proteins in the Male Reproductive Tract. Studies on Semenogelins, Beta-Microseminoprotein, and PC3-Secreted Microprotein

Sammanfattning: Human semen has several important constituents, including the prostate secreted proteins beta-microseminoprotein (MSP), prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), and the seminal-vesicle-derived coagulum proteins semenogelin I (SEMG1) and semenogelin II (SEMG2). The research underlying this thesis explored the evolution, expression and structure of seminal plasma proteins to provide further knowledge in the area of reproduction, particularly regarding MSP and the semenogelins. Several of the studies focused on two species of New World monkeys, that represent evolutionary intermediates between the rodents and humans, and work was also done to characterize a human MSP homologue, and obtain physiological data on human MSP. The results show that the cotton-top tamarin carries five genes for MSP, one of which exhibits transcriptional activity, and two are nonfunctional pseudogenes. Moreover, the closely related common marmoset has several MSP genes and at least three different forms of MSP in the ejaculate, which also contains semenogelins, but not PAP and PSA. In the marmoset, the genes for both SEMG1 and SEMG2 are transcribed in the seminal vesicles, and they are very similar due to gene conversion. Marmoset SEMG1 has two allelic variants, which differ by one 60-amino-acid repeat. The studies also revealed the existence of a previously unknown and highly conserved human gene with distant homology to the MSP gene. The protein encoded by this gene is designated PC3-secreted microprotein (PSMP), because it is expressed and secreted by the prostate cancer cell line PC-3, and it can also be detected in benign and malignant prostate tissues. An immunoassay for MSP was developed and used to measure the protein in serum and seminal plasma from young men. Correlations were found between the levels of MSP in seminal plasma and serum, and also between the concentrations of MSP, zinc and PSA in seminal plasma. Accordingly, we suggest that MSP in serum and semen can serve as a valid marker of prostate secretion.