The Cebpd (C/EBPδ) Gene Is Induced by Luteinizing Hormones in Ovarian Theca and Interstitial Cells But Is Not Essential for Mouse Ovary Function

A-Mei Huang,Mark Raffeld,Lane K Christenson,Esta Sterneck,Shikha Sharan,Martina Rudelius,Jan M Mcallister,Simon Williams

doi:10.1371/journal.pone.0001334

Abstract

The CCAAT/enhancer binding protein (CEBP) family of transcription factors includes five genes. In the ovary, both Cebpa and Cebpb are essential for granulosa cell function. In this study we have explored the role of the Cebpd gene in ovarian physiology by expression and functional studies. Here we report that Cebpd (C/EBPδ) is expressed in the mouse ovary in a highly restricted temporal and spatial pattern. In response to luteinizing hormone (LH/hCG), CEBPD expression is transiently induced in interstitial cells and in theca cells of follicles from the primary to pre-ovulatory stage, and overlaps in part with expression of the alpha-smooth muscle actin protein. Efficient down-regulation of CEBPD was dependent on a functional Cebpb gene. Proliferating human theca cells in culture also express Cebpd. Cells from patients with polycystic ovarian syndrome (PCOS) exhibited higher Cebpd expression levels. However, deletion of Cebpd in mice had no overt effect on ovarian physiology and reproductive function. Very little is known at present about the molecular mechanisms underlying theca/interstitial cell functions. The expression pattern of CEBPD reported here identifies a novel functional unit of mouse theca cells of primary through tertiary follicles responding to LH/hCG together with a subset of interstitial cells. This acute stimulation of CEBPD expression may be exploited to further characterize the hormonal regulation and function of theca and interstitial cells.

Highlights

The ovary is a complex organ undergoing regular phases of reorganization in response to a variety of intrinsic and extrinsic factors
Knockdown and targeted mutations have shown that both CEBPA and CEBPB are important for ovulation and Cebpb-deficient mice are sterile presumably due to a granulosa cell defect [8]
We used a combination of expression studies and genetic analysis to assess the function of CEBPD in the mouse ovary

Summary

Introduction

The ovary is a complex organ undergoing regular phases of reorganization in response to a variety of intrinsic and extrinsic factors. The main functional unit, the follicle is comprised of a central oocyte, mural and cumulus granulosa cell layers, and an outer layer of theca cells. The ovulatory surge of luteinizing hormone (LH), produced by the pituitary, triggers a series of dramatic morphological and physiological changes in the pre-ovulatory follicle, culminating in ovulation and subsequent differentiation of the follicular granulosa and theca cells into the luteal cells. Transcription factors known to act downstream of LH receptor activation include STAT1 and STAT5 [2], GATA4 [6], EGR1 [7], and the CCAAT/enhancer binding protein proteins CEBPA and CEBPB [8]

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Conclusion