Cleavage of prolactin by its target organs and the possible significance of this process.
An enzymatically cleaved form of rat prolactin (rPRL) was first described in 1980. This cleavage produces a molecule that consists of two chains of amino acids linked by a disulfide bond between two Cys residues. Reduction of that bond produces two fragments of 6 and 16 Kd. A considerable amount of information has accrued in recent years about the cleaved molecule and its 16-Kd fragment. The enzyme that cleaves the molecule is present in target tissues of PRL in rodents (e.g., mammary gland and ventral prostate), and the activity of the enzyme changes with the functional state of the mammary gland. Rat mammary PRL-cleaving activity is specific for rodent PRL, and the enzyme is localized in the stroma of that gland. The enzyme that cleaves rPRL is probably cathepsin D, and the sites of cleavage on the molecule have been identified. The cleaved form of rPRL has a high degree of activity in various assays, but it has reduced activity in radioimmunoassays. The 16-Kd fragment retains a significant degree of bioactivity in in vitro mitogenic assays, and specific binding sites for the fragment have been identified. Novel bioactivities for the cleaved form of rPRL and its 16-Kd fragment have been reported, and these molecules may account for the fact that bioassay estimates of PRL in rat serum are generally higher than are RIA measurements. Although the 16-Kd fragment has significant bioactivity, it contains only six of the fourteen residues that are thought to participate in the coupling of the intact hormone to its receptor. Cleaved rPRL is present in rat serum (but not in milk), but whether the 16-Kd fragment is formed in vivo has not yet been determined.
Nicoll
C S
CS
Department of Integrative Biology, University of California, Berkeley 94720-3140, USA.
D000818:Animals; D001665:Binding Sites; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology; D011388:Prolactin / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011981:Receptors, Prolactin / Q000378:metabolism
D010446:Peptide Fragments; D011981:Receptors, Prolactin; D011388:Prolactin