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Anti-prolactin (PRL) autoantibodies suppress PRL bioactivity in patients with macroprolactinaemia
Naoki Hattori1, Yasuhisa Nakayama, Kaori Kitagawa
1Department of Pharmacology, Kansai Medical University, Osaka, Japan. hattorin@takii.kmu.ac.jp
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.
Insights
Macroprolactinaemia, often caused by anti-prolactin autoantibodies, shows normal bioactivity in the Nb2 assay due to antibody dissociation. However, in vivo bioactivity is reduced, though monomeric prolactin retains full activity.
Area of Science:
- Endocrinology
- Reproductive Biology
- Clinical Biochemistry
Background:
- Macroprolactinaemia, frequently linked to anti-prolactin (PRL) autoantibodies, is a common cause of hyperprolactinaemia.
- Patients with macroprolactinaemia often lack typical hyperprolactinaemia symptoms despite elevated serum PRL levels.
- The discrepancy between measured and bioactive PRL in macroprolactinaemia requires investigation.
Purpose of the Study:
- To investigate the causes of the discrepancy between serum PRL levels and clinical presentation in macroprolactinaemia.
- To determine the true biological features and bioactivity of macroprolactin in patients with anti-PRL autoantibodies.
- To compare PRL bioactivity using different bioassays and assess the role of autoantibodies.
Main Methods:
- Studied sixteen patients with macroprolactinaemia caused by anti-PRL autoantibodies.
- Assessed PRL bioactivity using T47D cell phosphorylation of signal transducer and activator of transcription (Stat)5.
- Evaluated PRL bioactivity through Nb2 rat lymphoma cell proliferation assays.
Main Results:
- T47D bioassay showed significantly lower PRL bioactivity in sera with anti-PRL autoantibodies compared to controls.
- Acidification-induced dissociation of PRL from autoantibodies increased Stat5 phosphorylation.
- Nb2 bioassay revealed no significant difference in PRL bioactivity between sera with and without autoantibodies, with gradual free PRL increase over time.
Conclusions:
- The Nb2 bioassay overestimates macroprolactin bioactivity due to PRL dissociation from autoantibodies under prolonged incubation and dilute conditions.
- In vivo, macroprolactin bioactivity is reduced by anti-PRL autoantibodies.
- Monomeric PRL, once dissociated from autoantibodies, retains its full biological activity in patients with macroprolactinaemia.
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