Molecular mechanism for repression of 17α-hydroxylase expression and androstenedione production in granulosa cells

Satin S. Patel, Victor E. Beshay, Julian C. Escobar, Takashi Suzuki, Bruce R. Carr

研究成果: Article査読

28 被引用数 (Scopus)

抄録

Context: According to the traditional two-cell two-gonadotropin model of follicular steroidogenesis, androgen production arises exclusively from theca cells. The granulosa cells, in turn, utilize androstenedione and testosterone, which are aromatized into estrone and estradiol, respectively. Differential expression of the activator protein-1 (AP-1) transcription factor, c-fos, has been postulated to result in distinct patterns of steroidogenesis in the theca and granulosa cell compartments. Wehypothesize that c-fos functions to inhibit the production of 17α-hydroxylase 17,20 lyase (CYP17) in granulosa cells, thereby suppressing androgen synthesis. Objective: Our objective was to define the role of c-fos in the regulation of CYP17 production in granulosa cells. Design and Methods: Human luteinized granulosa (HGL5) cells were utilized for all experiments. The following techniques were used: mRNA extraction, steroid quantification, small interfering RNA silencing, microarray analysis, and immunohistochemistry. Results: Immunohistochemistry studies demonstrated significant staining of c-fos in the granulosa cell layer, but absent staining for CYP17. Conversely, the theca cell layer did not stain for c-fos, but staining was evident for CYP17. Treatment of HGL5 cells with the MAPK kinase inhibitor PD98059 resulted in an 11-fold increase in CYP17 mRNA levels. In c-fos gene silenced cells, CYP17 mRNA levels increased 8-fold. Androstenedione production was increased 13-fold after treatment with PD98059. Conclusions: These results suggest that the AP-1 transcription factor, c-fos, may be one of the factors responsible for CYP17 repression and hence suppression of androstenedione production in granulosa cells. This may provide an explanation for the lack of CYP17 in granulosa cells.

本文言語English
ページ(範囲)5163-5168
ページ数6
ジャーナルJournal of Clinical Endocrinology and Metabolism
94
12
DOI
出版ステータスPublished - 2009 12

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 内分泌学
  • 臨床生化学
  • 生化学、医学

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