Function and regulation of CCAAT/enhancer binding protein beta in Leydig cell development and steroidogenesis

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Title: Function and regulation of CCAAT/enhancer binding protein beta in Leydig cell development and steroidogenesis
Author: Nalbant, Demet
Abstract: Pituitary luteinizing hormone (LH ) is required for the development of multiple cell types in both the male and female reproductive systems . In particular , LH promotes differentiation of testicular Leydig cells and stimulates steroid production by Leydig cells in the testis , theca , granulosa and luteal cells in the ovary . We have been interested in identifying nuclear transcription factors that are targets of LH signaling pathways in Leydig cells and concentrated on CCAAT /enhancer binding protein beta (C /EBPp ) . Our initial studies showed that C /EBPp is expressed in a differentiation specific pattern whose expression is stimulated by LH /human chorionic gonadotropin (hCG ) and cyclic AMP (cAMP ) in Leydig cells . We hypothesized that C /EBPp plays an important role in LH regulated Leydig cell development and steroidogenic function . To assess the specific roles of C /EBPp in Leydig cell function we have analyzed the steroidogenic capacity of Leydig cells from C /EBPp -deficient mice generated by gene targeting . This study revealed that testosterone production in male C /EBPp deficient mice is severally compromised suggesting that C /EBPp is essential for complete functional differentiation of Leydig cells . In order to understand how LH effects on Leydig cell differentiation and /or function may be mediated through C /EBPp , we attempted to identify genetic control elements that control C /EBPp transcription in steroidogenic and non -steroidogenic cells . We identified an evolutionarily conserved , steroidogenic cell -specific , distal enhancer element located in the C /EBPp 5' -flanking region . Our studies suggest that the activity of the enhancer may be , at least in part , controlled by as yet uncharacterized nuclear factors specifically detected in nuclear extracts of steroidogenic cells . These studies set the stage for elucidation of the molecular mechanisms controlling C /EBPp expression in steroidogenic cells in general , and may aid in uncovering alternative LH -dependent signaling pathways critical for functional maturation of Leydig cells
URI: http : / /hdl .handle .net /2346 /16173
Date: 2002-08

Citation

Function and regulation of CCAAT/enhancer binding protein beta in Leydig cell development and steroidogenesis. Doctoral dissertation, Texas Tech University. Available electronically from http : / /hdl .handle .net /2346 /16173 .

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