Transcription of the fish Latent TGFbeta-binding protein gene is controlled by estrogen receptor alpha

In endocrine disruption a key role has been suggested for endocrine receptors, in particular the estrogen receptors (ERs), in the regulation by compounds mimicking natural hormones. The two ERs, ERalpha and ERbeta are transcription factors involved in the regulated expression of estrogen target genes and have been shown to play an essential role in mammalian ovary development. A similar role is to be expected for ERs in fish; little is, however, known in fish about genes regulated by ERs. To begin to address this, we here report the identification and characterization of a novel gene regulated by the fish ERalpha in response to 17beta-estradiol. This gene encodes a fish orthologue of the latent transforming growth factor beta binding protein 3 (LTBP-3) and was identified through a differential display approach from a rainbow trout gonad cell line (RTG-2-ERalpha). We show that the rainbow trout LTBP (rtLTBP-3) is ERalpha dependent and is upregulated 5-fold in response to 17beta-estradiol addition. The rtLTBP shows 61% amino acid similarity to human LTBP-3 and 48%, 44% and 41% to LTBP-1, LTBP-2 and LTBP-4, respectively. The highly conserved TB2 domain of rtLTBP shows 87% and 66% identity to the TB domains of human LTBP-3 and LTBP-1, respectively. LTBP plays a pivotal role in TGFbeta activation in mammals and the high degree of sequence similarity suggests a similar role in fish. This would represent a novel link between nuclear hormone receptors and growth factor (TGFbeta) mediated developmental processes, and show new aspects of the role of hormones in developmental biology and endocrine disruption.