Department of Physiology & Pathophysiology, University of Manitoba, Winnipeg, MB, Canada.
J Neuroendocrinol. 2020 Nov;32(11):e12859. doi: 10.1111/jne.12859. Epub 2020 Jun 5.
The four genes coding for placental members of the human (h) growth hormone (GH) family include two that code independently for placental lactogen (PL), also known as chorionic somatomammotrophin hormone, one that codes for placental growth hormone (PGH) and a pseudogene for which RNA but no protein product is reported. These genes are expressed preferentially in the villus syncytiotrophoblast of the placenta in pregnancy. In higher primates, the placental members, including hPL and PGH, are the result of multiple duplication events of the GH gene. This contrasts with rodents and ruminants, where PLs result from duplication of the prolactin (PRL) gene. Thus, unlike their mouse counterparts, the hPL and PGH hormones bind both lactogenic and somatogenic receptors with varying affinity. Roles influenced by nutrient availability in both metabolic control in pregnancy and maternal behaviour are supported. However, the effect maternal obesity has on the activation of placental members of the hGH gene family, particularly the expression and function of those genes, is poorly understood. Evidence from partially humanised hGH/PL transgenic mice indicates that both the remote upstream hPL locus control region (LCR) and more gene-related regulatory regions are required for placental expression in vivo. Furthermore, a specific pattern of interactions between the LCR and hPL gene promoter regions is detected in term placenta chromatin from women with a normal body mass index (BMI) in the range 18.5-25 kg m by chromosome conformation capture assay. This pattern is disrupted with maternal obesity (class II BMI > 35 kg m ) and associated with a > 40% decrease in term hPL RNA levels, as well as serum hPL but not PRL levels, during pregnancy. The relative importance of the chromosomal architecture and predicted properties for transcription factor participation in terms of hPL production and response to obesity are considered, based on comparison with components required for efficient human pituitary GH gene expression.
编码人（h）生长激素（GH）家族胎盘成员的四个基因包括两个独立编码胎盘催乳素（PL）的基因，也称为绒毛膜生长激素，一个编码胎盘生长激素（PGH）的基因和一个报道没有 RNA 但没有蛋白质产物的假基因。这些基因在妊娠期间优先在胎盘绒毛合体滋养层中表达。在高等灵长类动物中，包括 hPL 和 PGH 在内的胎盘成员是 GH 基因多次复制事件的结果。这与啮齿动物和反刍动物形成对比，PL 是催乳素（PRL）基因复制的结果。因此，与它们的小鼠对应物不同，hPL 和 PGH 激素以不同的亲和力结合催乳素和生长激素受体。支持受营养可用性影响的代谢控制和母性行为的作用。然而，母体肥胖对 hGH 基因家族胎盘成员的激活，特别是那些基因的表达和功能的影响，了解甚少。部分人源化 hGH/PL 转基因小鼠的证据表明，远程上游 hPL 基因座控制区（LCR）和更多基因相关调节区都需要在体内胎盘表达。此外，在正常体重指数（BMI）范围为 18.5-25kg/m 的妇女的足月胎盘染色质中，通过染色体构象捕获测定检测到 LCR 和 hPL 基因启动子区域之间特定的相互作用模式。这种模式在母体肥胖（BMI 类 II > 35kg/m）时被打乱，并与妊娠期间足月 hPL RNA 水平降低 > 40%相关，以及血清 hPL 但不是 PRL 水平降低。考虑到与有效人类垂体 GH 基因表达所需的成分进行比较，根据染色体结构和预测的转录因子参与 hPL 产生和对肥胖反应的特性的相对重要性。
