Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Busan, Gyeongsangnam 50463, Republic of Korea.
Department of Obstetrics and Gynecology, Biomedical Research Institute, School of Medicine, Pusan National University, Busan, Gyeongsangnam 49241, Republic of Korea.
Mol Med Rep. 2019 May;19(5):3903-3911. doi: 10.3892/mmr.2019.10048. Epub 2019 Mar 15.
Female sex steroid hormones, including estradiol (E2) and progesterone (P4), serve significant physiological roles in pregnancy. In particular, E2 and P4 influence placenta formation, maintain pregnancy and stimulate milk production. These hormones are produced by ovaries, adrenal glands and the placenta, of which the latter is a major endocrine organ during pregnancy. However, the mechanism of hormone production during pregnancy remains unclear. In the present study, the regulation of steroid hormones and steroidogenic enzymes was examined in human placenta according to gestational age. In human placental tissues, expression levels of steroidogenic enzymes were determined with reverse transcription‑quantitative polymerase chain reaction and western blotting. The mRNA and protein expression of CYP17A1, HSD17B3 and CYP19A1, which are associated with the synthesis of dehydroepiandrosterone (DHEA) and E2, was elevated at different gestational ages in human placenta. In addition, to evaluate the correlation between serum and placental‑produced hormones, steroid hormone levels, including pregnenolone (PG), DHEA, P4, testosterone (T) and E2, were examined in serum and placenta. Serum and placenta expression of DHEA and E2 increased with gestational age, whereas T and P4 were differently regulated in placenta and serum. To confirm the mechanism of steroidogenesis in vitro, placental BeWo cells were treated with E2 and P4, which are the most important hormones during pregnancy. The mRNA and protein expression of steroidogenic enzymes was significantly altered by E2 in vitro. These results demonstrated that concentration of steroid hormones was differently regulated by steroidogenic enzymes in the placenta depending on the type of the hormones, which may be critical to maintain pregnancy.
女性性激素,包括雌二醇(E2)和孕酮(P4),在妊娠中起着重要的生理作用。特别是,E2 和 P4 影响胎盘形成、维持妊娠和刺激乳汁分泌。这些激素由卵巢、肾上腺和胎盘产生,其中后者是妊娠期间的主要内分泌器官。然而,妊娠期间激素产生的机制尚不清楚。在本研究中,根据妊娠年龄检查了人胎盘中的甾体激素和甾体生成酶的调节。在人胎盘组织中,通过逆转录-定量聚合酶链反应和蛋白质印迹法测定甾体生成酶的表达水平。与脱氢表雄酮(DHEA)和 E2 合成相关的 CYP17A1、HSD17B3 和 CYP19A1 的 mRNA 和蛋白表达在人胎盘的不同妊娠年龄升高。此外,为了评估血清和胎盘产生的激素之间的相关性,在血清和胎盘检查了包括孕烯醇酮(PG)、DHEA、P4、睾酮(T)和 E2 在内的甾体激素水平。血清和胎盘 DHEA 和 E2 的表达随妊娠年龄而增加,而 T 和 P4 在胎盘和血清中的调节方式不同。为了在体外证实甾体生成的机制,用在妊娠期间最重要的激素 E2 和 P4 处理胎盘 BeWo 细胞。甾体生成酶的 mRNA 和蛋白表达在体外明显受 E2 影响。这些结果表明,在胎盘内,根据激素的类型,甾体激素的浓度通过甾体生成酶以不同的方式调节,这对于维持妊娠可能至关重要。