The Prolactin Gene is Expressed in the Hypothalamic-Neurohypophyseal System and the Protein is Processed Into a 14-kDa Fragment with Activity Like 16-kDa Prolactin

• Published in: Proceedings of the National Academy of Sciences - PNAS 1994-10, Vol.91 (22), p.10384-10388
• Main Authors: Clapp, Carmen, Torner, Luz, Gutierrez-Ospina, Gabriel, Alcantara, Eva, Lopez-Gomez, Francisco J., Nagano, Makoto, Kelly, Paul A., Mejia, Salvador, Morales, Miguel A., de la Escalera, Gonzalo Martinez
• Format: Article
• Language: English
• Subjects: Animals; Antiserum; Base Sequence; Biochemistry; Biological Assay; Blotting, Southern; Blotting, Western; Capillaries; Cattle; Cell Division - drug effects; Cerebrovascular Circulation; DNA Primers; DNA, Complementary; Endocrinology; Endothelial cells; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Exons; Female; Hormones; Hypothalamo-Hypophyseal System - metabolism; Immune Sera; Messenger RNA; Molecular Sequence Data; Molecular Weight; Molecules; Neurons; Peptide Fragments - analysis; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Pituitary Gland, Posterior - metabolism; Polymerase Chain Reaction; Posterior pituitary; Prolactin - analysis; Prolactin - biosynthesis; Prolactin - genetics; Protein Processing, Post-Translational; Proteins; Rats; Rats, Wistar; RNA; RNA, Messenger - analysis; Thymidine - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.22.10384

The 23-kDa form of prolactin (PRL) has been proposed to function as both a mature hormone and a prohormone precursor for different uniquely bioactive forms of the molecule. We have shown that the 16-kDa N-terminal fragment of PRL (16K PRL) inhibits angiogenesis via a specific receptor. In addition, 16K PRL stimulates natriuresis and diuresis in the rat, and kidney membranes contain high-affinity specific binding sites for this PRL fragment. 16K PRL can be derived from an enzymatically cleaved form of PRL (cleaved PRL). With the use of a specific 16K PRL antiserum, we have localized a 14-kDa immunoreactive protein in the paraventricular and supraoptic nuclei of the hypothalamus and in the neurohypophysis. Reverse transcription-polymerase chain reaction of RNA from isolated paraventricular nuclei showed the expression of the full-length PRL mRNA. The neurohypophysis was found to contain the enzymes that produce cleaved PRL, small amounts of PRL, and cleaved PRL. Medium conditioned by neurohypophyseal cultures, enriched with the 14-kDa immunoreactive protein, has antiangiogenic effects that are blocked by the 16K PRL antiserum. These results are consistent with the expression of PRL in the hypothalamic-neurohypophyseal system, and the preferential processing of the protein into a 14-kDa fragment with biological and immunological properties of 16K PRL.