GATA‐1 is a potential repressor of anti‐Müllerian hormone expression during the establishment of puberty in the mouse

Abstract

Anti-Müllerian hormone (AMH), also known as Müllerian inhibiting substance (MIS), is one of the earliest and best-known markers of Sertoli cell differentiation and is expressed until around puberty. The present study is aimed at the better understanding of the molecular pathways involved in testicular development and establishment of adult functions with regards to AMH regulation. We found, within the mouse AMH promoter, putative GATA motifs (A/T)GATA(A/G), known to be specifically bound by members of the GATA transcription factor family. We then carried out RNase protection assays and immunohistochemical techniques aimed at comparing precisely the chronological expression patterns of AMH and GATA-1, this latter being expressed in the testis after birth. Using both approaches we found an inverse and close relationship between AMH and GATA-1 mRNA and protein expression during the pre-pubertal period. These results allowed us to define a transitory 4-5-day period, starting from 3 dpp when both proteins are heterogeneously expressed in Sertoli cells and showed that the appearance of GATA-1 is associated with the decrease of AMH expression in these cells. Furthermore DNA-protein interaction in in vitro studies showed first that GATA-1 binds with various affinities on sites found in the AMH promoter and second that the proximity of the two strongest affinity sites leads to a synergistic binding effect. Altogether, the present study suggests that GATA-1 participates in AMH gene repression during the pre-pubertal period.

Mutated elements of a complex promoter (Amh) can help to demonstrate the role of certain elements in controlling differential gene expression

“…4.3 In some cases, mutation of a potential element leads to an increase in EGFP expression. For instance, mutation of the proxGata site, situated close to the start of transcription [13], led to an increased expression in all three cell lines: this is possibly compatible with the observation that the termination of most of Amh expression in males coincides with the start of GATA-1 expression [4]: however it must be borne in mind that there is a possibility of internecine competition between members of the Gata family. GATA-1 could be functionally inert blocking access of active members of the family to the proxGata element: Gata-4 is known to play a positive role in granulosa cells [7,21].…”

In vivo analysis of the regulation of the anti‐Müllerian hormone, as a marker of Sertoli cell differentiation during testicular development, reveals a multi‐step process

“…Shortly after birth, the orphan nuclear receptor DAX-1 is re-expressed in Sertoli cells (Tamai et al, 1996) and seems to act as a negative modulator of SF-1-mediated transactivation of the AMH promoter (Nachtigal et al, 1998). Complementary to this, we have shown that there is a potential involvement of the transcription factor GATA-1 in AMH gene down-regulation during the establishment of puberty (Beau et al, 2000). Taken together, these observations show that the regulation of the AMH gene is complex, probably being composed of at least three phases-initiation, maintenance, and repression (see Fig.…”

Long-Term Maintenance of Viable Adult Rat Sertoli Cells Able to Establish Testis Barrier Components and Function in Response to Androgens

“…As exemplarily shown for one SC cell line, PASC1, they were nearly 100% pure and express the SC-specific protein SOX9 as well as the epithelial genes transferrin and clusterin, which are characteristic for SCs [ 31 , 32 , 33 ]. Similarly, as shown for epithelial cells from other organs such as breast, prostate, colon, and lungs [ 15 , 51 , 52 ], the conditionally reprogrammed PASC1 maintained their differentiation even after passage 21 by expressing the SC-maturation gene GATA1 in contrast to a very weak expression of AMH, a typical marker for immature SCs [ 34 , 36 ]. Moreover, we could observe that the non-epithelial cells such as LCs and PCs are lost in the early passages as reported for non-epithelial cells from other tissues [ 14 , 15 ].…”