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

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

doi:10.1111/j.1365-2265.2006.02548.x

Cited by 29 publications

(23 citation statements)

References 40 publications

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“…For a long time, the large size of macroprolactin has been proposed to make it unable to cross capillary membranes to reach its target receptors, thus reducing its in vivo activity and explaining the attenuated clinical manifestations [1,[15][16][17][18]. However, results of recent studies have shown that macroprolactin has reduced activity toward its homologous receptor and this altered bioactivity may contribute to the absence of symptoms related to macroprolactin [19,20].…”

Section: Discussionmentioning

confidence: 97%

Prevalence of pituitary adenomas in macroprolactinemic patients may be higher than it is presumed

et al. 2011

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One form of prolactin (PRL) is macroprolactin with high molecular mass. Many macroprolactinemic patients have no pituitary adenomas and no clinical symptoms of hyperprolactinemia, it is controversial whether macroprolactinemia is a benign condition that does not need further investigation and treatment. In this study, we aimed to compare macroprolactinemic patients (group I) with the true hyperprolactinemic patients (group II) for the presence of pituitary adenoma. We investigated 161 patients with hyperprolactinemia, whose magnetic resonance imaging records of the pituitary were taken. All patients were questioned for irregular menses, infertility and examined for galactorrhea. Patients were screened for macroprolactinemia by polyethylene glycol precipitation, and a recovery of ≤40% and normal monomeric PRL level was taken as an indication of significant macroprolactinemia. Of 161 patients with hyperprolactinemia, 60 (37.26%) had macroprolactinemia. PRL levels of group II were lower than those of group I (P = 0.011), although monomeric PRL levels of group II were higher than those of group I (P = 0.0005). Of 60 macroprolactinemic patients, 16 (26.7%) had pituitary adenomas. The prevalence of pituitary adenomas was lower in group I, compared with group II (P = 0.0005). No significant differences were found between the prevalences of irregular menses and infertility of group I and II (P = 0.084, P = 0.361). Prevalence of galactorrhea in group I was lower than that in group II (P = 0.048). Prevalence of pituitary adenomas in macroprolactinemic patients is lower compared with the true hyperprolactinemic patients, but may be higher than that found in other recent studies and in the general population.

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Section: Discussionmentioning

confidence: 97%

Prevalence of pituitary adenomas in macroprolactinemic patients may be higher than it is presumed

et al. 2011

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“…One study examined the correlation between the Nb2 assay and a similar assay using human prolactin receptor. [31] When the predominant form of prolactin was monomeric, the two assays performed similarly; however, when high levels of macroprolactin were present, the Nb2 assay had higher levels than the human based assay. Second, while the bioactivity assay is primarily influenced by prolactin, proliferation also can be stimulated by growth hormone,[15, 26] although the concentrations of growth hormone must be very high to stimulate Nb2 cells and over 80% of the stimulation is due to prolactin.…”

Section: Discussionmentioning

confidence: 99%

Bioactive Prolactin Levels and Risk of Breast Cancer: A Nested Case–Control Study

Tworoger

Rice

Rosner

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Prolactin is a lactogenic hormone associated with breast cancer risk in prospective studies, which used immunoassays. The immunoassay captures multiple isoforms and may not fully reflect the biological activity of prolactin relevant to breast carcinogenesis. Methods We considered plasma bioactive prolactin levels measured by the Nb2 lymphoma cell bioassay, which is sensitive to the somatolactogenic activity of prolactin and growth hormone, within a nested case-control study of invasive breast cancer in the Nurses’ Health Studies (NHS/NHSII). We also considered associations with breast cancer risk factors. Results We had bioassay measures on 1329 cases and 1329 controls. Bioassay levels were inversely associated with parity (4+ vs. 0 children=−18%, p=0.01), body mass index (30+ vs. <22kg/m2=−16%, p<0.01), and age at menopause (53+ vs. 48yr=−18%, p=0.03) and positively with family history of breast cancer (yes vs. no=14%, p<0.01). The relative risk (RR) comparing the top versus bottom quartile of bioassay levels was 1.19 (95% confidence interval [CI]=0.94–1.51; p-trend=0.18). The association was suggestively stronger for postmenopausal (RR=1.36, 95%CI=0.93–1.98; p-trend=0.12) versus premenopausal women (RR=0.99, 95%CI=0.71–1.37, p-trend=0.71). There was an association for cases diagnosed <4 years after blood draw (RR=2.66, 95%CI=1.45–4.89, p-trend<0.01), but not for cases diagnosed later. We did not observe differential associations by estrogen receptor status or other tumor characteristics. Conclusions Our results show similar associations for prolactin levels measured by bioassay and by immunoassay with both breast cancer risk factors and risk. Impact Future work examining risk prediction model of breast cancer can use the immunoassay to accurately characterize risk.

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“…Macroprolactinemia is characterized by a lack of clinical symptoms of hyperprolactinemia and several studies using different PRL bioassay systems showed that the bioactivity of macroprolactin is low [32, 42, 43]. The epitope mapping using deleted PRL fragments revealed that the binding sites of PRL molecule to anti-PRL autoantibodies reside in N and C terminals of PRL [39].…”

Section: Pathogenic Significancementioning

confidence: 99%

Macroprolactinemia: Diagnostic, Clinical, and Pathogenic Significance

Shimatsu

Hattori

2012

Clinical and Developmental Immunology

105

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Macroprolactinemia is characterized by a large molecular mass of PRL (macroprolactin) as the main molecular form of PRL in sera, the frequent elevation of serum PRL (hyperprolactinemia), and the lack of symptoms. Macroprolactin is largely a complex of PRL with immunoglobulin G (IgG), especially anti-PRL autoantibodies. The prevalence of macroprolactinemia is 10–25% in patients with hyperprolactinemia and 3.7% in general population. There is no gender difference and a long-term followup demonstrates that macroprolactinemia develops before middle age and is likely a chronic condition. Polyethylene-glycol- (PEG-) precipitation method is widely used for screening macroprolactinemia, and gel filtration chromatography, protein A/G column, and I125-PRL binding studies are performed to confirm and clarify its nature. The cross-reactivity of macroprolactin varies widely according to the immunoassay systems. The epitope on PRL molecule recognized by the autoantibodies is located close to the binding site for PRL receptors, which may explain that macroprolactin has a lower biological activity. Hyperprolactinemia frequently seen in macroprolactinemic patients is due to the delayed clearance of autoantibody-bound PRL. When rats are immunized with rat pituitary PRL, anti-PRL autoantibodies are produced and hyperprolactinemia develops, mimicking macroprolactinemia in humans. Screening of macroprolactinemia is important for the differential diagnosis of hyperprolactinemia to avoid unnecessary examinations and treatments.

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

Cited by 29 publications

References 40 publications

Prevalence of pituitary adenomas in macroprolactinemic patients may be higher than it is presumed

Prevalence of pituitary adenomas in macroprolactinemic patients may be higher than it is presumed

Bioactive Prolactin Levels and Risk of Breast Cancer: A Nested Case–Control Study

Macroprolactinemia: Diagnostic, Clinical, and Pathogenic Significance

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