Regulation of androgen action during establishment of pregnancy

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   Figure 1

   Androgen:oestrogen balance and regulation of the endometrial microenvironment. Decidualisation is associated with changes in local metabolism and synthesis of bioactive androgens, which may be affected by changes in bioavailability of circulating steroid precursors. (A) Increased expression and activity of AKR1C3 early in decidualisation is associated with biosynthesis of testosterone, which is converted to potent androgen DHT by the action of SRD5A1 (Gibson et al. 2016). Testosterone and DHT produced by ESCs during decidualisation signal via an intracrine mechanism to regulate the early decidual response and impact on endometrial transcription of decidualisation and endometrial receptivity factors. (B) Local androgens promote time-sensitive changes in gene transcription during endometrial remodelling, including expression of the decidualisation marker IGFBP1 and the receptivity marker SPP1 (Gibson et al. 2016). Insufficient androgen signalling at this time may promote a transcriptional profile that is ‘out of phase’, which could impact on endometrial receptivity, blastocyst implantation and the establishment of pregnancy. (C) Regulation of testosterone bioavailability may also impact on the regulation of the endometrium by acting as a precursor to oestrogens. Following induction of aromatase expression in decidualised ESCs (Gibson et al. 2013), local oestrogens regulate immune-mediated vascular remodelling by altering the function of uNK cells in early pregnancy (Gibson et al. 2015).

• © 2016 Society for Endocrinology