Association between prolactin receptor expression and proliferation in the endometrium of obese women with polycystic ovary syndrome

Gynecol Endocrinol. 2020 Mar;36(3):226-232. doi: 10.1080/09513590.2019.1650343. Epub 2019 Aug 7.

Abstract

Polycystic ovary syndrome (PCOS) is associated with increased risk of endometrial cancer. There is growing evidence that prolactin and its receptor (PRLR) are involved in the development of cancer. We assessed endometrial expression of PRLR mRNA, and immunostaining of PRLR and the proliferation marker Ki67 on different cycle days in obese (OB-PCOS) and normal-weight women with PCOS and body mass index-matched controls. The OB-PCOS group underwent a 3 months lifestyle intervention. Prior to intervention, obese women with PCOS and controls had lower endometrial levels of PRLR mRNA in proliferative endometrium than the normal-weight groups (p < .05). After intervention, six OB-PCOS women had confirmed ovulation, while 12 remained anovulatory. Both these subgroups displayed higher immunostaining of PRLR in endometrial stroma, and in the anovulatory subgroup also increased Ki67, on cycle days 21-23 compared with controls (p < .05). In obese controls, the PRLR mRNA expression was decreased in secretory endometrium compared with proliferative endometrium (p = .004). A corresponding change within the cycle was not found in OB-PCOS women. Immunostaining of PRLR in the secretory phase correlated positively with Ki67 (p < .05) in the endometrium. These observations suggest that short-term lifestyle intervention can restore ovulation but not normalize PRLR expression in the endometrium of obese women with PCOS. Trial registration: ISRCTN, ISRCTN18400086, https://doi.org/10.1186/ISRCTN18400086.

Keywords: PCOS; endometrium; prolactin receptor; proliferation.

MeSH terms

  • Adult
  • Case-Control Studies
  • Cell Proliferation / genetics*
  • Diet, Reducing
  • Endometrium / metabolism*
  • Female
  • Follicular Phase / genetics
  • Follicular Phase / metabolism
  • Humans
  • Ki-67 Antigen / metabolism
  • Luteal Phase / genetics
  • Luteal Phase / metabolism
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / therapy
  • Ovulation
  • Polycystic Ovary Syndrome / genetics*
  • Polycystic Ovary Syndrome / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Prolactin / genetics*
  • Receptors, Prolactin / metabolism
  • Treatment Outcome
  • Weight Reduction Programs
  • Young Adult

Substances

  • Ki-67 Antigen
  • MKI67 protein, human
  • RNA, Messenger
  • Receptors, Prolactin