Transcription Factors in the Regulation of Leydig Cell Gene Expression and Function

Abstract

Cell differentiation and acquisition of specialized functions are inherent steps in events that lead to normal tissue development and function. These processes require accurate temporal, tissue, and cell-specific activation or repression of gene transcription. This is achieved by complex interactions between transcription factors that form a unique combinatorial code in each specialized cell type and in response to different physiological signals. Transcription factors typically act by binding to short, nucleotide-specific DNA sequences located in the promoter region of target genes. In males, Leydig cells play a crucial role in sex differentiation, health, and reproductive function from embryonic life to adulthood. To better understand the molecular mechanisms regulating Leydig cell differentiation and function, several transcription factors important to Leydig cells have been identified, including some previously unknown to this specialized cell type. This mini review summarizes the current knowledge on transcription factors in fetal and adult Leydig cells, describing their roles and mechanisms of action.

A Short Promoter Region Containing Conserved Regulatory Motifs Is Required for Steroidogenic Acute Regulatory Protein (Star) Gene Expression in the Mouse Testis

“…Testicular STAR expression and activity are acutely regulated by the gonadotropin LH (reviewed in [ 13 , 20 ]). LH stimulation also induces steroidogenesis in the testis, which triggers numerous signaling pathways, which in turn can activate several transcription factors including GATA4 (reviewed in [ 2 ]). We therefore hypothesized that acute Star regulation might be impaired in testes of p Star Δ19-GATAmut mice.…”

“…The regulation of testicular steroidogenesis is complex and involves many regulatory molecules and mechanisms such as luteinizing hormone (LH), its signaling pathways, and the factors that interpret these signals [ 1 ]. The latter include most notably transcription factors acting on the expression of genes that encode steroidogenic enzymes and other proteins involved in the biosynthesis of testosterone (reviewed in [ 2 , 3 ]).…”

Effect of melatonin on steroidogenesis-related enzyme expression and testosterone synthesis following CoCl 2 -induced hypoxia in TM3 Leydig cells

“…Moreover, GATA-4 protein de ciency effects the steroidogenesis metabolic pathways. The StAR gene includes a regulatory sequence recognized by GATA-4 proteins in the testes [15]. Studies have shown that steroidogenesis is affected by HIF1α protein and disruption of HIF1α protein signaling can relate to steroidogenesis disorders and reducing male reproductive function [5,36].…”

“…Testicular Leydig cells are located in the interstitial space of the seminiferous tubules in the testis. They are responsible for the synthesis and release of testosterone in mammals [15]. The steroidogenic acute regulatory (StAR) protein is involved in the transport of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane and the enzyme CYP11A1 converts cholesterol to pregnenolone in the inner membrane of the mitochondria.…”

Insights Into the Roles of GATA Factors in Mammalian Testis Development and the Control of Fetal Testis Gene Expression

“…FLCs are proposed to derive from progenitor cells originating within the adreno-gonadal primordium and other sources within the mesonephros, neural crest cells, coelomic epithelium [reviewed in ( 72 )]. Many transcription factors have been implicated in FLC differentiation and function [reviewed in ( 73 , 74 )]. GATA4 appears to play an integral role in both of these processes.…”