Application of new homologous in vitro bioassays for human lactogens to assess the actual bioactivity of human prolactin isoforms in hyperprolactinaemic patients

Authors: Leaños-Miranda, Alfredo; Cárdenas-Mondragón, Guadalupe; Rivera-Leaños, Roxana; Ulloa-Aguirre, Alfredo; Goffin, Vincent

Source: Clinical Endocrinology, Volume 65, Number 2, August 2006 , pp. 146-153(8)

Publisher: Wiley-Blackwell

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Abstract:

Summary Background 

 Prolactin (PRL) plays a central role in mammary gland development and lactation. Due to its molecular heterogeneity, measurement of PRL immunoreactivity does not necessarily reflect its intrinsic bioactivity. For many years the Nb2 rat lymphoma cell bioassay has been the only reference bioassay for human lactogens. This bioassay, however, does not always correlate with the clinical features found in some patients exhibiting normal or elevated immunoreactive serum PRL concentrations. Objectives 

 (1) To determine the concentrations of bioactive PRL in serum samples from individuals with normoprolactinaemia or with different forms of hyperprolactinaemia using two recently described homologous in vitro bioassays (i.e. a transcriptional bioassay in HEK-293 cells and a proliferation assay in Ba/F3 cells); and (2) to compare these results with those generated by the classical Nb2 cell bioassay. Design 

 Cross-sectional study. Setting 

 An institutional biomedical research laboratory. Participants 

 Ten patients with symptomatic hyperprolactinaemia due to prolactinoma, 11 patients with asymptomatic hyperprolactinaemia and macroprolactinaemia, and nine normal women. Main outcome measures 

 Measurement of immunoreactive and bioactive concentrations of serum PRL. Results 

 Samples from normal women and patients with tumoral hyperprolactinaemia due to prolactinoma exhibited similar within-group concentration values of bioactive and immunoreactive serum PRL when tested by the three bioassays and the immunoradiometric assay employed. By contrast, measurement of bioactive PRL in samples from patients with macroprolactinaemia revealed that macroprolactin was poorly active in the homologous receptor bioassays, while it was more active in the Nb2 bioassay. Conclusions 

 The reduced bioactivity of PRL in patients with macroprolactinaemia may further explain the absence of clinical features of hyperprolactinaemia in these individuals. In addition, our findings indicate that species-specificity and sensitivity of the bioassays are determinant factors in the measurement of the intrinsic biological activity of circulating PRL.

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2265.2006.02548.x

Affiliations: 1: Research Unit in Reproductive Medicine, Hospital de Ginecología y Obstetricia `Luis Castelazo Ayala', Instituto Mexicano del Seguro Social, México D.F., Mexico,

Publication date: 2006-08-01

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