Hormonal Regulation of Kallikreins

Steroid hormones, acting through their receptors, play important roles in the normal development and function of many organs. In addition, they are involved in the pathogenesis of many types of cancer [146]. Several reports confirmed that many kallikreins are under steroid hormone regulation in endocrine-related tissues and cell lines [100, 147-155].

An interesting observation is the tissue-specific pattern of hormonal regulation of several of these genes in different tissues. For example, KLK4 is upregulated by androgen in prostate and breast cancer cell lines [148] and by estrogen in endometrial cancer cell lines [147]. Also, KLK12 was found to be upregulated by androgens and progestins in prostate cancer cell lines and by estrogens and progestins in breast cancer cell lines [156]. KLK14 and KLK15 are mainly regulated by androgens. Recent preliminary kinetic and blocking experiments indicate that this upregulation is mediated through the androgen receptor [155, 157].

In general, it can be concluded that most, if not all, kallikrein genes are regulated by steroid hormones, either predominantly by androgens or by estrogens/progestins/glucocorticoids. Because most of the data have been generated in cell lines, which contain variable amounts of various steroid hormone receptors, it will be very interesting to delineate the hormonal regulation of these genes in vivo. Manipulation of kallikrein gene expression by steroids may have therapeutic potential in some diseases such as cancer, psoriasis, or others.

Recently, Palmer et al., working with human colon cancer cell lines, reported dramatic up-regulation of kallikreins 6 and 10 by 1a, 25-dihydroxyvitamin D3 [158]. This finding raises the possibility that some kallikreins could be regulated by a multitude of nuclear receptors.

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