TELEOST FTZ-F1 HOMOLOG AND ITS SPLICING VARIANT DETERMINE THE EXPRESSION OF THE SALMON GONADOTROPIN II-BETA SUBUNIT GENE

Steroidogenic factor 1, a member of the fushi tarazu factor 1 (FTZ-F1) subfamily of nuclear receptors, is a key regulator in mammalian repro duction. From an embryonic complementary DNA library, the zebrafish ho molog of FTZ-F1 (zFF1A) and an alternatively spliced variant (zFF1B) w ere isolated, zFF1B represented a C-terminally truncated version of zF F1A. Whole mount in situ hybridization and reverse transcriptase-PCR a nalysis revealed that both zFF1A and B transcripts were present in the developing pituitaries, adult fish brain, gonads, and liver, albeit z FF1B messenger RNA was absent in testis. Comparison of the primary seq uences of zFF1 with those of other FTZ-F1 subfamily members showed a c lose structural relationship between the mouse liver receptor homolog, which activated the alpha(1)-fetoprotein gene in rodent liver. Howeve r, similar to mouse steroidogenic factor 1, zFF1A regulated chinook sa lmon gonadotropin II beta subunit gene expression. On the contrary, zF F1B, which could bind a consensus gonadotrope-specific element with an affinity similar to that of zFF1A, lacked both the trans-activation f unction and synergistic interaction with the estrogen receptor. Furthe rmore, cotransfection studies in HeLa cells showed that zFF1B was a st rong competitor for the action of zFF1A on the chinook salmon gonadotr opin II beta subunit gene promoter. Our investigation suggests that 1) zFF1 represents an ancestor protein of the vertebrate FTZ-F1 homologs ; 2) the antagonistic relationship between zFF1A and -B may dictate th e expression of the FTZ-F1 target genes in a variety of tissues, inclu ding the pituitary; and 3) the naturally occurring zFF1B provides evid ence that the C-terminal portion of zFF1A (80 amino acid residues) con tains a major trans-activation function and a protein-protein interfac e.