FKBP4 (
FKBP52) and FKBP5 (FKBP51) are
progestin receptor (PR) co-chaperone
proteins that enhance and inhibit, respectively,
progestin-mediated transcription by PR. Here, we examined
FKBP4 and FKBP5 expression in the eutopic endometrium of fertile women with
endometriosis and effects of
FKBP4 and FKBP5 on the decidualization of human endometrial stromal cells (HESCs), and assessed HOXA10 regulation of
FKBP4. Expression of
FKBP4 mRNA was increased in the late proliferative phase and remained elevated throughout the secretory phase. FKBP5 expression was low and remained constant throughout the menstrual cycle. Compared with controls,
FKBP4 mRNA expression was decreased in the endometrium of women with
endometriosis, whereas no significant
endometriosis-related change was seen for FKBP5. Cultured HESCs were treated with either
FKBP4 or FKBP5
siRNA and then decidualized by incubation with
progesterone (P(4)) and
8-bromoadenosine cAMP. Treatment of HESCs with
FKBP4 siRNA resulted in 60% lower IGFBP1 expression. In contrast, incubation with FKBP5
siRNA did not significantly decrease IGFBP1 expression during in vitro decidualization. HOXA10 and
FKBP4 expression increased in parallel during in vitro decidualization. In HESCs, overexpressed HOXA10 enhanced
FKBP4 mRNA and
protein levels, whereas HOXA10 knockdown decreased
FKBP4 mRNA and
protein levels compared with controls. Similarly, during in vitro decidualization,
FKBP4 expression was decreased in HOXA10-silenced cells. Enhanced HOXA10 expression in HESCs elicits a decidualization mediating increase in
FKBP4 expression. The findings are consistent with the observation that women with
endometriosis have diminished
FKBP4 expression leading to impaired decidualization and
infertility. The P(4) resistance seen in
endometriosis may be mediated through HOXA10-regulated
FKBP4 expression.