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

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

摘要

多囊卵巢综合征（PCOS）与子宫内膜癌的风险增加有关。越来越多的证据表明催乳素及其受体（PRLR）参与了癌症的发展。我们评估了肥胖PCOS（OB-PCOS）、正常体重PCOS以及体重指数相匹配的对照组, 月经周期的不同时期PRLR mRNA的表达以及PRLR和增殖标志物Ki67的免疫染色。OB-PCOS组进行了3个月的生活方式干预。干预之前, OB-PCOS和对照组的肥胖女性增殖期子宫内膜中PRLR mRNA的表达水平低于正常体重女性（p <0.05）。干预后, 有6名OB-PCOS女性确认有排卵, 而12名仍无排卵。与对照组相比, 在月经周期的第21∼23天, 这两个亚组在子宫内膜间质中均表现出PRLR较高的免疫染色, 而在无排卵亚组中, Ki67也升高（p <0.05）。在肥胖对照组中, 与增殖期子宫内膜相比, 分泌期子宫内膜中PRLR mRNA表达降低（p = 0.004）。在OB-PCOS女性中未发现月经周期内的相应变化。在分泌期的子宫内膜中PRLR免疫染色与Ki67正相关（p <0.05）。这些观察结果表明, 短期生活方式干预可恢复PCOS肥胖女性的排卵, 但不能使子宫内膜PRLR表达正常。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• PCOS
• endometrium
• prolactin receptor
• proliferation

Acknowledgements

We are thankful to Åsa Nybacka, Department of Clinical Nutrition and Dietetics, for guiding and helping our female volunteers to change their diets. We are grateful to Lotta Blomberg, Siv Rödin Andersson, and Berit Legerstam at the Women’s Clinical Health Research Unit and Britt Masironi at the Department of Women’s and Children’s Health for skillful technical assistance.

Availability of data and material: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This study was supported financially by the Swedish Research Council under Grant ALH 20324; Swedish Cancer Society under Grant 150785; Karolinska Institutet, and the Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and Karolinska Institutet under Grant ALH, LS.