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  • Title: Anti-prolactin (PRL) autoantibodies suppress PRL bioactivity in patients with macroprolactinaemia.
    Author: Hattori N, Nakayama Y, Kitagawa K, Ishihara T, Saiki Y, Inagaki C.
    Journal: Clin Endocrinol (Oxf); 2008 Jan; 68(1):72-6. PubMed ID: 17681026.
    Abstract:
    OBJECTIVE: Macroprolactinaemia, mainly caused by anti-prolactin (PRL) autoantibodies, is frequently found in patients with hyperprolactinaemia. Characteristically, these patients lack clinical symptoms of hyperprolactinaemia, but the serum bioactive PRL concentrations in vitro measured by the Nb2 bioassay are usually high. In this study, we investigated the causes of the discrepancy and the true biological features of macroprolactin. SUBJECTS AND METHODS: Sixteen patients with macroprolactinaemia due to anti-PRL autoantibodies were studied. PRL bioactivity was determined by the phosphorylation of signal transducer and activator of transcription (Stat)5 in T47D human breast cancer cells and the proliferation of Nb2 rat lymphoma cells. RESULTS: PRL bioactivity by the T47D bioassay, expressed as the density of the band of phosphorylated Stat5/immunoreactive PRL, was significantly lower in sera containing anti-PRL autoantibodies (2.4 +/- 1.1) than in control sera (7.2 +/- 3.1). Dissociation of PRL from the autoantibodies by acidification resulted in an increase in phosphorylated Stat5. PRL bioactivity by the Nb2 bioassay was not significantly different between sera with and without anti-PRL autoantibodies, and free PRL in the medium gradually increased during the incubation in a time-dependent manner in sera containing anti-PRL autoantibodies. CONCLUSIONS: We conclude that the level of bioactivity of macroprolactin in the Nb2 bioassay is normal due to dissociation of PRL from the autoantibodies as a result of the longer incubation and more dilute assay conditions than in the T47D bioassay. The bioactivity of macroprolactin is low in vivo due to anti-PRL autoantibodies, but monomeric PRL dissociated from the autoantibodies retains full biological activity in patients with macroprolactinaemia.
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