Serum and Urine Tissue Kallikrein Concentrations in Male-To-Female Transsexuals Treated with Antiandrogens and Estrogens (Endocrinology and Metabolism‪)‬

The human tissue kallikrein family includes 15 genes (KLK1 to KLK15) [6] clustered in tandem on chromosome 19813.4. These genes encode for 15 kallikrein proteins (hK1 to hK15), [7] which are all secreted serine proteases. Groups of kallikreins are expressed in many tissues, including the salivary glands, the central nervous system, the skin, endocrine glands such as the testis and ovaries, and hormone-dependent tissues such as the breast, endometrium, and prostate (1). Among the 15 kallikreins, pancreatic/ renal kallikrein (W1), glandular kallikrein (hK2), and prostate-specific antigen (hK3; PSA) have been studied the most, and specific biological functions have been assigned to them. The primary function of hK1 is the release of lysyl-bradykinin, a vasoactive peptide (2), hK2 activates the proform of hK3, and hK3 is involved in semen liquefaction, increasing the motility of spermatozoa (3). The remaining kallikreins are less well characterized, but they are implicated in a wide range of physiologic functions, from regulation of cell growth to tissue remodeling (1, 4-6). hK3, better known as PSA, is a valuable tumor marker of prostate cancer (7). The potential significance of the other kallikreins in tumor biology has been reviewed (1, 4-6, 8). Accumulating evidence indicates that, in addition to hK2 and hK3, many other members of the human kallikrein gene family are also implicated in carcinogenesis, in particular, in endocrine-dependent malignancies. Recent reports suggest a possible role for kallikreins in controlling vital elements of tumor biology, such as apoptosis, angiogenesis, and tumor metastasis, by cleavage of critical substrates such as growth factors, hormones, receptors, or extracellular matrix proteins (5, 9,10). Furthermore, many kallikreins are known to be up- or down-regulated by steroid hormones in breast and prostate cancer cell lines and may represent important new tumor markers for the diagnosis, monitoring, and treatment of endocrine-dependent malignancies (4, 5, 9, 11,12).