  Lampreys are jawless fish that evolved about 550 million years ago at the
base of the vertebrate line. Modern lampreys contain a corticoid receptor (CR),
the common ancestor of the glucocorticoid receptor (GR) and mineralocorticoid
receptor (MR), which first appear in cartilaginous fish, such as sharks. Until
recently, 344 amino acids at the amino terminus of adult lamprey CR were not
present in the lamprey CR sequence in GenBank. A search of the recently
sequenced lamprey germline genome identified two CR sequences, CR1 and CR2,
containing the 344 previously un-identified amino acids at the amino terminus.
CR1 also contains a novel four amino acid insertion in the DNA-binding domain
(DBD). We studied corticosteroid activation of CR1 and CR2 and found their
strongest response was to 11-deoxycorticosterone and 11-deoxycortisol, the two
circulating corticosteroids in lamprey. Based on steroid specificity, both CRs
are close to elephant shark MR and distant from elephant shark GR. HEK293 cells
transfected with full-length CR1 or CR2 and the MMTV promoter have about 3-fold
higher steroid-mediated activation compared to HEK293 cells transfected with
these CRs and the TAT3 promoter. Deletion of the amino-terminal domain (NTD) of
lamprey CR1 and CR2 to form truncated CRs decreased transcriptional activation
by about 70% in HEK293 cells transfected with MMTV, but increased transcription
by about 6-fold in cells transfected with TAT3, indicating that the promoter
has an important effect on NTD regulation of CR transcription by
corticosteroids.

Biomolecules