Endocrine Abstracts

The propensity for prolactin (PRL) to form high molecular mass complexes in serum is well described. Macroprolactin (mPRL), a PRL-immunoglobulin complex (>100 kDa), is the predominant form of PRL in up to 20% of patients with hyperprolactinaemia. Big PRL (bPRL, 40–50 kDa) is a ubiquitous, minor component of serum PRL rarely the major immunoreactive form, the nature of which is unclear. Using gel filtration chromatography (GFC) we have investigated the relative abundance of mPRL, bPRL and monomeric PRL in hyperprolactinaemic sera. To assess the relationship between levels of mPRL, bPRL and monomeric PRL, we have studied 26 hyperprolactinaemic serum samples with no mPRL but with bPRL (6–29% of total PRL) and 26 samples with mPRL (10–84% of total PRL, mean 62%). We find a clear correlation between bPRL and monomeric PRL levels (r²=0.653); but no correlation between bPRL and mPRL (r²=0.09). We have further studied bPRL in a pregnant patient with all three prolactin forms. Re-chromatography of the mPRL fraction showed that mPRL dissociates in vitro to bPRL (48%) and monomeric PRL (20%). Adsorption of serum with protein G removed all mPRL and most but not all of bPRL, suggesting that bPRL may be derived from the dissociation of mPRL. In another, non-pregnant, subject with 82% mPRL, re-chromatography of mPRL again revealed dissociation to bPRL (25%) and monomeric PRL. Our findings suggest that bPRL detected by GFC may be from two sources with which it is in dynamic equilibrium; one, the predominant contributor in the absence of mPRL, is monomeric PRL in the circulation, and the other is in vitro dissociation of mPRL during chromatography. These findings may explain the variable immuno-reactivity of macroprolactin in different prolactin immunoassay systems, as the degree of dilution and affinity of the capture antibody may affect dissociation of the mPRL complex.