Tissue kallikrein is a serine protease thought to be involved in the generation of bioactive peptide kinins from kininogen in many organs such as
the kidneys, colon, salivary glands, pancreas, and blood vessels. Unlike pepsin, members of the glandular kallikrein subfamily of
serine proteases demonstrate a high degree of substrate specificity. The true physiologic role of specific kallikreins is often unrelated to the kininogenase activity.
NCBI Summary:
Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Its protein product is a protease present in seminal plasma. It is thought to function normally in the liquefaction of seminal coagulum, presumably by hydrolysis of the high molecular mass seminal vesicle protein. Serum level of this protein, called PSA in the clinical setting, is useful in the diagnosis and monitoring of prostatic carcinoma. Alternate splicing of this gene generates several transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
General function
Enzyme, Hydrolase, Peptidase/Protease
Comment
Cellular localization
Secreted
Comment
Diagnostic value of prostate-specific antigen (PSA) and free prostate specific antigen (fPSA) in women with ovulatory and anovulatory polycystic ovary syndrome. UKINC K et al. (2009) Diagnosis of polycystic ovary syndrome (PCOS) is very difficult in women with ovulatory cycles. We assessed the diagnostic value of prostate-specific antigen (PSA) and free prostate-specific antigen (fPSA) in women with ovulatory or anovulatory PCOS. Study group consisted of 62 women with PCOS and 35 healthy female controls. PCOS group was divided into two subgroups as anovulatory (n = 42; 68%, Group A) and ovulatory group (n = 20; 32%, Group B). A cut-off level of PSA and fPSA was established for the sensitivity, specificity, positive likelihood ratio, area under curve, diagnostic accuracy, and positive and negative predictive values of diagnosis of PCOS. In group A, a PSA level of greater than 10 pg/ml yielded a sensitivity of 73.2%, a specificity of 80%, and a diagnostic accuracy of 73%, with a positive predictive value of 88.2% and a negative predictive value of 59.3%. An fPSA level of greater than 2.1 pg/ml yielded a sensitivity of 71.2%, a specificity of 80.4%, and a diagnostic accuracy of 87%, with a positive predictive value of 87.2% and a negative predictive value of 58.4%. In group B, a PSA level of greater than 10 pg/ml yielded a sensitivity of 65%, a specificity of 80%, and a diagnostic accuracy of 73%, with a positive predictive value of 76.5% and a negative predictive value of 69.6%. An fPSA level of greater than 2.1 pg/ml yielded a sensitivity of 65.4%, a specificity of 80.4%, and a diagnostic accuracy of 87%, with a positive predictive value of 75.5% and a negative predictive value of 68.4%. Circulating androgens and hirsutism are independently associated with the degrees of PSA and fPSA in PCOS women. Increased plasma levels of PSA (>10 pg/ml) and fPSA (>2.1 pg/ml) could be helpful as a diagnostic tool for women with ovulatory or anovulatory PCOS.//////////////////
Ovarian function
Ovulation
Comment
Prostate specific antigen (PSA) in diagnosis of polycystic ovarian syndrome - a new insight. Rudnicka E et al. (2016) Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder and cause of androgen excess in women. Prostate specific antigen (PSA) could be a new marker of hyperandrogenism in PCOS. The aim of the study was to assess the concentration PSA (total PSA - TPSA and free PSA - fPSA) in 165 patients with PCOS and 40 healthy female controls, the relationship between PSA (TPSA and fPSA) and hormonal parameters and to determine the performance of PSA in diagnosis of PCOS. Total PSA was higher in PCOS group versus controls. The fPSA was below the lower detection levels among all patients. The median value of FAI was 4.31 in PCOS patients versus 1.79 in controls, p < 0.001. There was a correlation of TPSA and tT (r= 0.173, p = 0.027) and TPSA and FAI (r = 0.2603, p = 0.001). AUC for FAI was 82.1%, threshold 2.56 nmol/l, for tT AUC 80.5%, threshold 0.54 ng/ml, for TPSA AUC 66.3%, threshold 0.005 ng/ml. The ROC analysis for A AUC 62.7%, threshold 3.95 ng/ml. PCOS women have higher serum concentration of TPSA than controls. TPSA positively correlate with T and FAI, which is the best marker for hyperandrogenic states and has better accuracy for tT and total PSA serum levels in diagnostic of PCOS.//////////////////
Holland AM, et al reported kallikrein gene expression in the gonadotrophin-stimulated
rat ovary.
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The kallikreins (KLKs) are a highly conserved multi-gene family of serine
proteases that are expressed in a wide variety of tissues and act on a diverse
range of substrates. KLK-like enzyme activity has variously been reported to
increase or decrease during the period leading up to ovulation in the equine
chorionic gonadotrophin (eCG)primed, human chorionic gonadotrophin
(hCG)-stimulated immature rat ovary. They used a gene-specific
RT-PCR/Southern hybridisation strategy to delineate the expression patterns
of six of the individual KLK genes expressed in the rat ovary (rKLK1-3 and
rKLK7-9) and have identified three broad patterns of expression in the
eCG/hCG-stimulated ovary in which there is either a post-eCG
increase/pre-ovulatory decrease in rKLK expression (rKLK1, rKLK3), a
peri-ovulatory decrease in expression (rKLK2, rKLK8) or a relatively
unchanged pattern of expression (rKLK7, rKLK9). In addition to clarifying
the earlier biochemical studies, these findings support a differential role for the
individual KLKs in the ovulatory process.
Is prostate-specific antigen a potential new marker of androgen excess in polycystic ovary syndrome? Vural B et al. Aim: To determine whether serum prostate-specific antigen (PSA) levels are increased in polycystic ovary syndrome (PCOS) and the possibility of PSA to be used as a diagnostic marker of hyperandrogenism in females. Methods: A total of 43 women with PCOS and 43 age-matched healthy females were recruited in this prospective case-control study. The subjects were compared by means of demographic parameters, hormonal and metabolic measures and serum PSA levels. The correlations between this marker and a wide variety of hormonal, biochemical, anthropometric measures were evaluated. Student's t-test, chi(2)-test and Spearman's correlation analysis were used for the statistical analysis where appropriate. Statistical significance was assumed with a value of P < 0.05. Results: Mean body mass index, waist/hip ratio, Ferriman-Gallwey scores (FG), lutenizing hormone/follicle stimulating hormone ratio, insulin resistance, serum triglycerides and very low density lipoprotein levels were demonstrated to be significantly higher in PCOS (P = 0.02, P = 0.008, P = 0.001, P = 0.001, P = 0.007, P = 0.001, P = 0.01, respectively). Total testosterone (TT), dehydroepiandrosteronesulfate (DHEAS) levels appeared to be significantly higher in PCOS (P = 0.002, P = 0.001, respectively). Serum PSA levels were found to be significantly higher in PCOS (PSA: 0.026 +/- 0.023 ng/mL in PCOS, PSA: 0.009 +/- 0.008 ng/mL in control cases, P < 0.001). Sex hormone binding globulin (SHBG) was significantly lower in the subjects with PCOS (P < 0.001). Additionally, positive correlations between PSA and FG scores (r: 0.417, P = 0.001), PSA and TT (r: 0.456, P = 0.03) and between PSA and DHEAS (r: 0.268, P = 0.02) were found. A negative correlation between SHBG and PSA was apparent (r : -0.40, P = 0.04). Conclusion: PSA is a well-established tumor marker of prostatic adenocarcinoma. It is also shown to be produced by extraprostatic tissues and fluids. As the gene expression of PSA is upregulated by the androgens and progestins in hormonally responsive tissues, hyperandrogenic syndromes such as PCOS may be associated with elevated serum PSA levels. PSA appears to be a promising marker of endogenous androgen excess in females suffering from PCOS.