Anti-prolactin (PRL) autoantibodies cause asymptomatic hyperprolactinemia: bioassay and clearance studies of PRL-immunoglobulin G complex.
The causes of hyperprolactinemia are varied, but some cases are classified as "idiopathic" because of unknown causes. We examined whether anti-prolactin (PRL) autoantibodies can cause hyperprolactinemia, especially the asymptomatic type. Serum PRL in four women with anti-PRL autoantibodies and five control patients with prolactinoma was characterized by a sensitive enzyme immunoassay, Nb2-bioassay, gel chromatography, affinity chromatography for immunoglobulin G (IgG), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under nonreducing conditions, and clearance studies using anesthetized rats. In four women with anti-PRL autoantibodies, serum immunoreactive PRL concentrations were elevated (326 +/- 216 micrograms/L, normal < 30 micrograms/L), and PRL (84 +/- 5.5%) mostly consisted of the large molecular form in which a significant amount of 23 kDa PRL (60.6 +/- 14.7%) was noncovalently bound to IgG. Although three of the four women lacked clinical symptoms of hyperprolactinemia such as amenorrhea and galactorrhea, the IgG-bound PRL was fully bioactive in vitro. It was cleared more slowly from circulation than free PRL. The data suggest that PRL forms a complex with IgG, and this probably results in delayed clearance of PRL and leads to hyperprolactinemia in women with anti-PRL autoantibodies.
Hattori
N
N
Department of Pharmacology, Kansai Medical University, Osaka, Japan.
Inagaki
C
C
D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000502:physiology*; D001681:Biological Assay; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000276:immunology*; D007074:Immunoglobulin G / Q000378:metabolism*; D008297:Male; D011388:Prolactin / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D001323:Autoantibodies; D007074:Immunoglobulin G; D011388:Prolactin