CONTEXT: Macroprolactinemia is a frequent finding in hyperprolactinemic individuals, usually without clinical impact. Data on biological activity of macroprolactin (bbPRL) are 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 prolactin (PRL) receptor (PRLR) species specificity. OBJECTIVE: The objective of the study was to 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 Ba/F-LLP bioassays. Both groups were followed up at the neuroendocrinology outpatients' clinic. MAIN OUTCOME MEASURE: Biological activity of bbPRL presented in the two bioassays was measured. RESULTS: In group I, no patient had hypogonadism. Mean ratio bioactivity to immunoactivity of bbPRL in the Nb2 assay was 0.69. There was no dose-response in 15 of the 18 samples tested in Ba/F-LLP assay. In group II, three patients had galactorrhea and all five had hypogonadism. Mean ratio bioactivity to immunoactivity of monomeric PRL samples was 1.35 in Nb2 and 0.91 in Ba/F-LLP assay. CONCLUSION: Whereas 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 because it is not observed in the human PRLR-mediated assay, consistent with the apparent absence of bioactivity in vivo.
CONTEXT: Macroprolactinemia is a frequent finding in hyperprolactinemic individuals, usually without clinical impact. Data on biological activity of macroprolactin (bbPRL) are controversial and mostly based on a heterologous ratNb2 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 prolactin (PRL) receptor (PRLR) species specificity. OBJECTIVE: The objective of the study was to characterize the bioactivity of bbPRL in a homologous bioassay: Ba/F-3 cells stably expressing the humanPRLR. DESIGN/SETTING/PATIENTS: Chromatography-purified bbPRL from macroprolactinemic individuals (group I, n = 18) and monomeric PRL from hyperprolactinemicpatients without macroprolactinemia (group II, n = 5) were tested in Nb2 and Ba/F-LLP bioassays. Both groups were followed up at the neuroendocrinology outpatients' clinic. MAIN OUTCOME MEASURE: Biological activity of bbPRL presented in the two bioassays was measured. RESULTS: In group I, no patient had hypogonadism. Mean ratio bioactivity to immunoactivity of bbPRL in the Nb2 assay was 0.69. There was no dose-response in 15 of the 18 samples tested in Ba/F-LLP assay. In group II, three patients had galactorrhea and all five had hypogonadism. Mean ratio bioactivity to immunoactivity of monomeric PRL samples was 1.35 in Nb2 and 0.91 in Ba/F-LLP assay. CONCLUSION: Whereas 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 because it is not observed in the humanPRLR-mediated assay, consistent with the apparent absence of bioactivity in vivo.
Authors: L Vilar; M C Freitas; L A Naves; L A Casulari; M Azevedo; R Montenegro; A I Barros; M Faria; G C Nascimento; J G Lima; L H Nóbrega; T P Cruz; A Mota; A Ramos; A Violante; A Lamounier Filho; M R Gadelha; M A Czepielewski; A Glezer; M D Bronstein Journal: J Endocrinol Invest Date: 2008-05 Impact factor: 4.256
Authors: Herbert Rodrigues Goulart; Fernanda dos Santos Arthuso; Marcos Vinicius Nucci Capone; Taís Lima de Oliveira; Paolo Bartolini; Carlos Roberto Jorge Soares Journal: J Biomed Biotechnol Date: 2010-06-16
Authors: Lucio Vilar; Luciana Ansaneli Naves; Luiz Augusto Casulari; Monalisa Ferreira Azevedo; José Luciano Albuquerque; Fabiano Marcel Serfaty; Flavia R Pinho Barbosa; Antonio Ribeiro de Oliveira; Renan Magalhães Montenegro; Renan Magalhães Montenegro; Alberto José Santos Ramos; Manuel Dos Santos Faria; Nina Rosa C Musolino; Monica R Gadelha; Cesar Luiz Boguszewski; Marcello D Bronstein Journal: Pituitary Date: 2010-09 Impact factor: 4.107