We previously found that prostate-specific antigen (PSA) expression in
the female breast is regulated by steroid hormones and their receptor
s. We have now examined whether the PSA concentration in serum changes
during the menstrual cycle of healthy women. Among 14 women studied,
3 had serum PSA greater than or equal to 4 ng/L; their changes in PSA
content during the menstrual cycle were studied in 7 informative cycle
s. We found that PSA concentrations in serum are highest during the mi
d-to late follicular phase, drop continuously with a hair-life of 3-5
days between the late follicular phase and mid-cycle, and reach a mini
mum during the mid-to late luteal phase. PSA changes do not correlate
with changes in lutropin (LH), follitropin (FSH), or estradiol concent
rations. However, PSA peaks seem to follow the progesterone concentrat
ion peaks, with a delay of 10-12 days. Sera of some volunteers were te
sted for their ability to upregulate PSA protein and PSA mRNA in a tis
sue culture system based on the T-47D breast carcinoma cell line. Only
sera obtained during the mid-to late luteal phase were able to upregu
late the PSA mRNA and protein. In stimulation experiments in vitro, pr
ogesterone, but not LII, FSH, estradiol, human chorionic gonadotropin,
prolactin, or growth hormone was able to upregulate PSA mRNA and prot
ein in the T-47D cell line. These data suggest that PSA is produced in
a cyclical manner during the menstrual cycle.