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Submitted on August 12, 2005
Accepted on December 20, 2005
Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Laboratory for Cellular and Molecular Endocrinology - LIM25, Division of Endocrinology and Metabolism, Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Biotechnology Department, IPEN-CNEN, Brazil; Fleury Laboratory, Section of Endocrinology, Brazil; Université Paris Descartes, Faculté de Médecine; INSERM U584, site Necker, 156 rue de Vaugirard Paris
* To whom correspondence should be addressed. E-mail: mdbronstein{at}uol.com.br.
Context: Macroprolactinemia is a frequent finding in hyperprolactinemic individuals, usually without clinical impact. Data on biological activity of macroprolactin (bbPRL) is controversial and mostly based on a heterologous rat Nb2 cell bioassay. Biological activity of bbPRL observed in vitro but not in vivo may be due to its high molecular weight preventing its passage through capillary barrier. Alternatively, bbPRL bioactivity may differ depending on the PRL receptor (PRLR) species specificity.
Objective: Characterize the bioactivity of bbPRL in a homologous bioassay: Ba/F-3 cells stably expressing the human PRLR.
Design/Setting/Patients: Chromatography-purified bbPRL from macroprolactinemic individuals (Group I, n = 18) and monomeric PRL from hyperprolactinemic patients without macroprolactinemia (Group II, n = 5) were tested in Nb2 and in Ba/F-LLP bioassays. Both groups were followed at the neuroendocrinology outpatients' clinic.
Main Outcome Measure: Biological activity of bbPRL presented in the two bioassays.
Results: Group I: no patient had hypogonadism. Mean ratio bioactivity/immunoactivity (BA/IA) of bbPRL in the Nb2 assay was 0.69. There was no dose-response in 15 out of the 18 samples tested in Ba/F-LLP assay. Group II: three patients had galactorrhea and all five had hypogonadism. Mean ratio BA/IA of monomeric PRL samples was 1.35 in Nb2 and 0.91 in Ba/F-LLP assay.
Conclusion: While both bioassays achieve similar results with respect to monomeric PRL activity, our results indicate that the activity displayed by bbPRL toward the rat receptor may be inappropriate since it is not observed in the human-PRLR mediated assay, consistent with the apparent absence of bioactivity in vivo.
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