The semenogelins: proteins with functions beyond reproduction?

Abstract

The coagulum proteins of human semen, semenogelins I and II, are secreted in abundance by the seminal vesicles. Their function in reproduction is poorly understood as they are rapidly degraded in ejaculated semen. However, more recent results indicate that it is time to put the semenogelins in a broader physiological perspective that goes beyond reproduction and fertility.

Seminal plasma proteins in prostatic carcinoma: increased nuclear semenogelin I expression is a predictor of biochemical recurrence after radical prostatectomy

“…In contrast to well-recognized physiologic functions of semenogelins and eppin in the male reproductive system [1][2][3][4][5][6][7], the role of these seminal plasma proteins in human malignancies remains unclear. Only a few studies have shown the expression of semenogelins in malignancies, including lung carcinomas, melanoma, and leukemias [11,12].…”

“…Furthermore, preoperative serum levels of PSA were significantly higher in patients with n-SgI-positive tumor than in those with n-SgI-negative tumor, suggesting SgI induces PSA secretion from prostate cancer. Because PSA physiologically degrades semenogelins in semen [1,2], it is possible that the increase in PSA levels may, at least partially, represent an attempt to target semenogelins rather than tumor progression.…”

“…SgI and SgII are highly expressed in the seminal vesicles as well as in other male genital organs such as vas deferens, epididymis, and prostate [4]. In addition, previous studies showed semenogelin expression in nongenital organs such as the trachea, salivary gland, pancreas, kidney, and retina [4,5], suggesting a physiologic role of these proteins as modulators of zinc-dependent proteases throughout the body [1,2].…”

“…Semenogelins I (SgI) (∼50 kd consisting of 439 amino acids) and II (SgII) (∼63 kd consisting of 559 amino acids with 78% homology to SgI) constitute the major structural proteins in human semen and are well-known to contribute to sperm clotting [1]. After ejaculation, these proteins are degraded into smaller (5-20 kd) fragments by prostatespecific antigen (PSA), resulting in clotted gel liquefaction and release of the trapped spermatozoa [2].…”

Proteolytic Activity of Prostate-Specific Antigen (PSA) towards Protein Substrates and Effect of Peptides Stimulating PSA Activity

“…While semenogelins I and II are considered to be the physiological substrates of PSA [16], [53], several other protein substrates have previously been reported to be degraded by PSA [9]. These proteins or their proteolytic fragments may either promote or inhibit cancer progression, e.g., the cleavage of fibronectin and laminin may be involved in cell invasion [25], [26], IGFBP-3 is associated with cell proliferation [44], [54], galectin-3 is involved in several processes including cell adhesion, proliferation, apoptosis and angiogenesis [55], [56] and plasminogen-derived angiostatin-like fragments inhibit angiogenesis [20].…”