4,5) Prolactin can be found in the circulation in one of three isoforms based on its molecular weight: monomeric PRL (small PRL; molecular weight 23 kDa), dimeric PRL (medium PRL; molecular weight 50-60 kDa), and polymeric PRL [large PRL/ macroprolactin (maPRL); molecular weight 150-170 kDa).
They demonstrated the bioactivity of macroprolactin component in vitro and suggested that the absence of in vivo bioactivity might be the result of the high molecular mass of the complex preventing passage through the capillary endothelium to its target cells (4).
In some individuals, as in the case reported in this issue by Khandwala et al, macroprolactin is the predominant form of circulating immunoreactive PRL (macroprolactinemia) and, if the cause is not recognized, the coincidence of apparent hyperprolactinemia and symptoms of the hyperprolactinemic syndrome can lead to misdiagnosis and mistreatment, unnecessary concern for patient and physician and waste of healthcare resources.
Big prolactin (60 kDa) and macroprolactin (150 kDa), which are present in serum in varying quantities, can cause apparent hyperprolactinemia, but they have no clinical importance because they exhibit little biological activity.
These include a monomer with a molecular mass of 23 kDa, which accounts for approximately 85% of PRL present in normal individuals, a 50 kDa species accounting for 10% to 15% of total PRL, and a small but variable amount of a high molecular mass form (150-170 kDa) termed "big big" prolactin or macroprolactin (1-5).
The most common form in healthy persons and in most patients with hyperprolactinemia is a monomeric prolactin (Mr 23 000), but higher molecular mass forms such as big prolactin (Mr 60 000) and big-big prolactin, or macroprolactin (Mr 150 000), sometimes predominate (1-4).