Taylor H S, Arici A, Olive D, Igarashi P
Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
J Clin Invest. 1998 Apr 1;101(7):1379-84. doi: 10.1172/JCI1057.
Hox genes are well-known transcriptional regulators that play an essential role in directing embryonic development. Mice that are homozygous for a targeted disruption of the Hoxa10 gene exhibit uterine factor infertility. We have recently demonstrated that HOXA10 is expressed in the adult human uterus. To examine expression of HOXA10 during the menstrual cycle, Northern blot analysis and in situ hybridization were performed. Expression of HOXA10 dramatically increased during the midsecretory phase of the menstrual cycle, corresponding to the time of implantation and increase in circulating progesterone. Expression of HOXA10 in cultured endometrial cells was stimulated by estrogen or progesterone. Stimulation of HOXA10 by progesterone was concentration-dependent within the physiologic range, and the effect of estrogen was inhibited by cycloheximide. These results identify sex steroids as novel regulators of HOX gene expression. HOXA10 may have an important function in regulating endometrial development during the menstrual cycle and in establishing conditions necessary for implantation in the human.
Hox基因是众所周知的转录调节因子,在指导胚胎发育中起重要作用。Hoxa10基因靶向破坏的纯合子小鼠表现出子宫因素不孕症。我们最近证明HOXA10在成年女性子宫中表达。为了检测月经周期中HOXA10的表达,进行了Northern印迹分析和原位杂交。HOXA10的表达在月经周期的分泌中期显著增加,这与着床时间和循环孕酮增加相对应。雌激素或孕酮可刺激培养的子宫内膜细胞中HOXA10的表达。在生理范围内,孕酮对HOXA10的刺激呈浓度依赖性,雌激素的作用被放线菌酮抑制。这些结果确定性类固醇是HOX基因表达的新型调节因子。HOXA10可能在调节月经周期中的子宫内膜发育以及建立人类着床所需条件方面具有重要功能。