Macroprolactin; high molecular mass forms of circulating prolactin

Ann Clin Biochem 2005;42:175-192
© 2005 Association for Clinical Biochemistry


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M N Fahie-Wilson,
R John and
A R Ellis

Department of Clinical Biochemistry, Southend Hospital, Westcliff-on-Sea, Essex SS0 0RY, UK;
Department of Medical Biochemistry, University Hospital of Wales, Cardiff CF14 4XW, UK;
Department of Clinical Biochemistry, UK NEQAS for Peptide Hormones and Related Substances, Royal Infirmary, Edinburgh EH16 4SA, UK

Two high molecular mass forms of prolactin (PRL) in serum have been identified by gel filtration chromatography (GFC): macroprolactin (big-big PRL, > 100 kDa) and big PRL (40-60 kDa). Macroprolactin has a variable composition and structure, but is most frequently a complex of PRL and IgG, with a molecular mass of 150-170 kDa. It is formed in the circulation following pituitary secretion of monomeric PRL but has a longer half-life, and the PRL in the complex remains reactive to a variable extent in immunoassays. In the majority of subjects little or no macroprolactin can be detected in serum, but in some individuals it may be the predominant immunoreactive component of circulating PRL and the cause of apparent hyperprolactinaemia. Owing to its high molecular mass, macroprolactin appears to be confined to the intravascular compartment and much evidence indicates that it has minimal bioactivity in vivo and is not of pathological significance. Nevertheless, hyperprolactinaemia due to macroprolactin can lead to diagnostic confusion and unnecessary further investigation and treatment if it is not recognized as such. Macroprolactin is a common cause of apparent hyperprolactinaemia with some assays and it is essential that laboratories introduce screening programmes to examine samples with elevated total immunoreactive PRL for the presence of macroprolactin and determine the monomeric PRL component which is known to be bioactive in vivo. A numberof screening tests have been described; that based on the precipitationof macroprolactin with polyethylene glycol has been the mostwidely validated and applied. The reference technique of GFCshould be available for confirmation and further investigationof samples, giving equivocal results in screening tests.

In comparison with macroprolactin, little is known about bigPRL. It is a more consistent component of total serum PRL butrarely, if ever, the cause of hyperprolactinaemia. Further researchis required into the nature of macroprolactin and big PRL, therelationships between high molecular mass forms of PRL, andtheir clinical significance.

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