Kr üppel-like factor 4 plays a role in the luteal transition in steroidogenesis by down-regulating Cyp19A1 expression.

Krüppel-like factor 4 plays a role in the luteal transition in steroidogenesis by down-regulating Cyp19A1 expression. Am J Physiol Endocrinol Metab. 2019 Apr 02;: Authors: Choi H, Ryu KY, Roh J Abstract The transition from granulosa cell to luteal cell involves a change from estrogen production to predominantly progesterone production. We analyzed the role of Krüppel-like factor 4 (Klf4), a transcriptional repressor used to generate pluripotent cells, in that transition. After luteinizing hormone/human chorionic gonadotropin (LH/hCG) treatment of preovulatory follicles, a major but transient increase in Klf4 transcript levels was detected. Therefore we enquired whether Klf4 is involved in the rapid decline of aromatase, the key estrogen-producing enzyme, using preovulatory granulosa cells (GCs) obtained from PMSG-primed immature rat ovaries. Cyp19A1 expression in GCs transfected with FLAG- Klf4 or Klf4-specific siRNA was analyzed by real-time PCR and immunofluorescence staining. Cyp19A1 decreased when Klf4 was overexpressed, and Cyp19A1 and estradiol biosynthesis increased when Klf4 was knocked down. The mechanism by which Klf4 regulates Cyp19A1 expression was investigated using Cyp19A1 promoter-luciferase reporter assays and ChIP assays. The results revealed that the SF1-binding motif, but not the Sp1 binding element or the CACCC motif, was required for Klf4-mediated repression of Cyp19A1 promoter activity. Here, we showed that Kl...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research