Abstract
Members of the pre-B-cell leukemia transcription factor (PBX) family of homeoproteins are mainly known for their involvement in hematopoietic cell differentiation and in the development of leukemia. The four PBX proteins, PBX1, PBX2, PBX3 and PBX4, belong to the three amino acid loop extension (TALE) superfamily of homeoproteins which are important transcriptional cofactors in several developmental processes involving homeobox (HOX) factors. Mutations in the human PBX1 gene are responsible for cases of gonadal dysgenesis with absence of male sex differentiation while Pbx1 inactivation in the mouse causes a failure in Leydig cell differentiation and function. However, no data is available regarding the expression profile of this transcription factor in the testis. To fill this knowledge gap, we have characterized PBX1 expression during mouse testicular development. Real time PCRs and Western blots confirmed the presence Pbx1 mRNA and PBX1 protein in different Leydig and Sertoli cell lines. The cellular localization of the PBX1 protein was determined by immunohistochemistry and immunofluorescence on mouse testis sections at different embryonic and postnatal developmental stages. PBX1 was detected in interstitial cells and in peritubular myoid cells from embryonic life until puberty. Most interstitial cells expressing PBX1 do not express the Leydig cell marker CYP17A1, indicating that they are not differentiated and steroidogenically active Leydig cells. In adults, PBX1 was mainly detected in Sertoli cells. The presence of PBX1 in different somatic cell populations during testicular development further supports a direct role for this transcription factor in testis cell differentiation and in male reproductive function.
Highlights
The testis is responsible for the production of gametes and for the secretion of sexual hormones that are essential for proper male reproductive development, growth, and function
Further acquisition of a male phenotype is strictly regulated by three hormones produced by the fetal testis: anti-Müllerian hormone (AMH) secreted by Sertoli cells, and testosterone and Insulin-like 3 (INSL3) both produced by Leydig cells
Results are the mean of three individual experiments each performed in duplicate (±SEM). (B) Specificity of the αPBX1-2-3-4 was determined by Western blot using nuclear extracts from HeLa cells mock transfected (CTL) or transfected with expression vectors for PBX1, PBX2 or PBX3 as indicated. (C) Western blot analyses of PBX1 protein in Leydig (MA-10, MLTC-1, TM3, LC-540, R2C) and Sertoli (MSC-1, 15P-1) cell lines using two different anti22 sera: αPBX1: top panel, αPBX1-2-3-4: middle panel
Summary
The testis is responsible for the production of gametes and for the secretion of sexual hormones that are essential for proper male reproductive development, growth, and function. Further acquisition of a male phenotype is strictly regulated by three hormones produced by the fetal testis: anti-Müllerian hormone (AMH) secreted by Sertoli cells, and testosterone and Insulin-like 3 (INSL3) both produced by Leydig cells. Steroid hormones which include testosterone secreted by Leydig cells and its more potent derivative dihydrotestosterone (DHT), are responsible for masculinization of the male fetus. They induce Wolffian duct differentiation into the epididymis, vas deferens, and seminal vesicles in addition to promoting development of the external genitalia and accessory sex glands. INSL3, a Leydig cells-secreted peptide belonging to the insulin/relaxin/growth factor family, regulates the first phase of the testicular descent during fetal life [6,7] and bone metabolism in adults [8]
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