5'-Heterogeneity in human progesterone receptor transcripts predicts a new amino-terminal truncated "C"-receptor and...

Human progesterone receptors (PR) are thought to comprise two naturally occurring hormone-binding proteins: 94-kDa A-receptors and 120-kDa B-receptors. In this paper we present evidence for a third human PR, an N-terminally truncated, 45- to 50-kDa species, termed the C-receptor. To determine the translational origin of B- and A-receptors we mapped the multiple messages that code for human PR by Northern blot analyses, using a series of oligonucleotides and cDNA fragment probes corresponding to different regions of the PR message. In addition to the six transcripts of 2.5, 3.2, 4.5, 5.2, 6.1, and 11.4 kilobases (kb) originally described, we found that the 11.4-kb species is a complex of four bands that we have termed I-IV. Analysis of poly(A)+ RNA derived from T47Dv human breast cancer cells using a variety of 5'-specific probes has identified three separate structural classes of human PR transcripts, indicating extensive 5'-termini heterogeneity. Class A messages, the 2.5- and 5.2-kb species, lack the sequences surrounding AUGB (codon 1), which is the translation initiation site for B-receptors, but contain AUGA (codon 165), the initiation site for A-receptors, and, therefore, potentially encode only the latter. Class B messages, consisting of the 3.2-, 4.5-, and 6.1-kb species as well as bands I and II of the 11.4-kb complex contain both AUGB and AUGA and could encode both receptor forms.(ABSTRACT TRUNCATED AT 250 WORDS)