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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Oct 25;91(22):10384–10388. doi: 10.1073/pnas.91.22.10384

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.

C Clapp 1, L Torner 1, G Gutiérrez-Ospina 1, E Alcántara 1, F J López-Gómez 1, M Nagano 1, P A Kelly 1, S Mejía 1, M A Morales 1, G Martínez de la Escalera 1
PMCID: PMC45024  PMID: 7937959

Abstract

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.

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Selected References

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  1. Andries M., Tilemans D., Denef C. Isolation of cleaved prolactin variants that stimulate DNA synthesis in specific cell types in rat pituitary cell aggregates in culture. Biochem J. 1992 Jan 15;281(Pt 2):393–400. doi: 10.1042/bj2810393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baldocchi R. A., Tan L., King D. S., Nicoll C. S. Mass spectrometric analysis of the fragments produced by cleavage and reduction of rat prolactin: evidence that the cleaving enzyme is cathepsin D. Endocrinology. 1993 Aug;133(2):935–938. doi: 10.1210/endo.133.2.8344226. [DOI] [PubMed] [Google Scholar]
  3. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  4. Clapp C. Analysis of the proteolytic cleavage of prolactin by the mammary gland and liver of the rat: characterization of the cleaved and 16K forms. Endocrinology. 1987 Dec;121(6):2055–2064. doi: 10.1210/endo-121-6-2055. [DOI] [PubMed] [Google Scholar]
  5. Clapp C., Martial J. A., Guzman R. C., Rentier-Delure F., Weiner R. I. The 16-kilodalton N-terminal fragment of human prolactin is a potent inhibitor of angiogenesis. Endocrinology. 1993 Sep;133(3):1292–1299. doi: 10.1210/endo.133.3.7689950. [DOI] [PubMed] [Google Scholar]
  6. Clapp C., Sears P. S., Nicoll C. S. Binding studies with intact rat prolactin and a 16K fragment of the hormone. Endocrinology. 1989 Aug;125(2):1054–1059. doi: 10.1210/endo-125-2-1054. [DOI] [PubMed] [Google Scholar]
  7. Clapp C., Sears P. S., Russell D. H., Richards J., Levay-Young B. K., Nicoll C. S. Biological and immunological characterization of cleaved and 16K forms of rat prolactin. Endocrinology. 1988 Jun;122(6):2892–2898. doi: 10.1210/endo-122-6-2892. [DOI] [PubMed] [Google Scholar]
  8. Clapp C., Weiner R. I. A specific, high affinity, saturable binding site for the 16-kilodalton fragment of prolactin on capillary endothelial cells. Endocrinology. 1992 Mar;130(3):1380–1386. doi: 10.1210/endo.130.3.1311239. [DOI] [PubMed] [Google Scholar]
  9. Cole E. S., Nichols E. H., Lauziere K., Edmunds T., McPherson J. M. Characterization of the microheterogeneity of recombinant primate prolactin: implications for posttranslational modifications of the hormone in vivo. Endocrinology. 1991 Nov;129(5):2639–2646. doi: 10.1210/endo-129-5-2639. [DOI] [PubMed] [Google Scholar]
  10. Compton M. M., Witorsch R. J. Proteolytic degradation and modification of rat prolactin by subcellular fractions of the rat ventral prostate gland. Endocrinology. 1984 Aug;115(2):476–484. doi: 10.1210/endo-115-2-476. [DOI] [PubMed] [Google Scholar]
  11. DeVito W. J. Heterogeneity of immunoreactive prolactin in the rat brain. Biochem Biophys Res Commun. 1988 Jan 29;150(2):599–604. doi: 10.1016/0006-291x(88)90435-4. [DOI] [PubMed] [Google Scholar]
  12. Emanuele N. V., Jurgens J. K., Halloran M. M., Tentler J. J., Lawrence A. M., Kelley M. R. The rat prolactin gene is expressed in brain tissue: detection of normal and alternatively spliced prolactin messenger RNA. Mol Endocrinol. 1992 Jan;6(1):35–42. doi: 10.1210/mend.6.1.1738369. [DOI] [PubMed] [Google Scholar]
  13. Emanuele N. V., Metcalfe L., Wallock L., Tentler J., Hagen T. C., Beer C. T., Martinson D., Gout P. W., Kirsteins L., Lawrence A. M. Hypothalamic prolactin: characterization by radioimmunoassay and bioassay and response to hypophysectomy and restraint stress. Neuroendocrinology. 1986;44(2):217–221. doi: 10.1159/000124648. [DOI] [PubMed] [Google Scholar]
  14. Ferrara N., Clapp C., Weiner R. The 16K fragment of prolactin specifically inhibits basal or fibroblast growth factor stimulated growth of capillary endothelial cells. Endocrinology. 1991 Aug;129(2):896–900. doi: 10.1210/endo-129-2-896. [DOI] [PubMed] [Google Scholar]
  15. Ferrara N., Houck K., Jakeman L., Leung D. W. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev. 1992 Feb;13(1):18–32. doi: 10.1210/edrv-13-1-18. [DOI] [PubMed] [Google Scholar]
  16. Hamakubo T., Furuta H., Ichimura M., Appalsamy M., Mosqueda-Garcia R., Robertson D., Inagami T. A Na pump inhibitor from bovine posterior pituitary: purification, structure determination and its cardiovascular effect in rat. Biochem Biophys Res Commun. 1992 Dec 15;189(2):691–696. doi: 10.1016/0006-291x(92)92256-w. [DOI] [PubMed] [Google Scholar]
  17. Harlan R. E., Scammell J. G. Absence of pituitary prolactin epitopes in immunoreactive prolactin of rat brain. J Histochem Cytochem. 1991 Feb;39(2):221–224. doi: 10.1177/39.2.1702799. [DOI] [PubMed] [Google Scholar]
  18. Harlan R. E., Shivers B. D., Fox S. R., Kaplove K. A., Schachter B. S., Pfaff D. W. Distribution and partial characterization of immunoreactive prolactin in the rat brain. Neuroendocrinology. 1989 Jan;49(1):7–22. doi: 10.1159/000125085. [DOI] [PubMed] [Google Scholar]
  19. Montgomery D. W., Shen G. K., Ulrich E. D., Steiner L. L., Parrish P. R., Zukoski C. F. Human thymocytes express a prolactin-like messenger ribonucleic acid and synthesize bioactive prolactin-like proteins. Endocrinology. 1992 Dec;131(6):3019–3026. doi: 10.1210/endo.131.6.1446637. [DOI] [PubMed] [Google Scholar]
  20. Nicoll C. S. Ontogeny and evolution of prolactin's functions. Fed Proc. 1980 Jun;39(8):2563–2566. [PubMed] [Google Scholar]
  21. Palkovits M. Punch sampling biopsy technique. Methods Enzymol. 1983;103:368–376. doi: 10.1016/s0076-6879(83)03025-6. [DOI] [PubMed] [Google Scholar]
  22. Russell D. H. New aspects of prolactin and immunity: a lymphocyte-derived prolactin-like product and nuclear protein kinase C activation. Trends Pharmacol Sci. 1989 Jan;10(1):40–44. doi: 10.1016/0165-6147(89)90106-5. [DOI] [PubMed] [Google Scholar]
  23. Swanson L. W., Sawchenko P. E. Hypothalamic integration: organization of the paraventricular and supraoptic nuclei. Annu Rev Neurosci. 1983;6:269–324. doi: 10.1146/annurev.ne.06.030183.001413. [DOI] [PubMed] [Google Scholar]
  24. Toubeau G., Desclin J., Parmentier M., Pasteels J. L. Cellular localization of a prolactin-like antigen in the rat brain. J Endocrinol. 1979 Nov;83(2):261–266. doi: 10.1677/joe.0.0830261. [DOI] [PubMed] [Google Scholar]
  25. de Wardener H. E., Clarkson E. M. Concept of natriuretic hormone. Physiol Rev. 1985 Jul;65(3):658–759. doi: 10.1152/physrev.1985.65.3.658. [DOI] [PubMed] [Google Scholar]

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