Endocrine Abstracts

Macroprolactin, a circulating complex of monomeric prolactin together with an autoantibody, is commonly encountered in the course of endocrine investigations. It is generally agreed macroprolactin exhibits reduced bioactivity in vivo since individuals who harbour the complex do not demonstrate the classic clinical signs or symptoms characteristic of true hyperprolactinaemia. The aim of this study was to compare the relative potency of purified preparations of macroprolactin to that of monomeric prolactin using an in vitro bioassay.

Macroprolactin and monomeric prolactin were purified by gel filtration chromatography from the sera of 10 macroprolactinaemic patients with total prolactin levels of 2,193 plus/minus 1,659 milliunits per litre (mean plus/minus SD) and monomeric levels of 300 plus/minus 131 milliunits per litre. The purified proteins were each tested for bioactivity using the Nb2 cell bioassay.

Both monomeric prolactin and macroprolactin were seen to induced a mitogenic response in Nb2 cells with macroprolactin exhibiting, on average, 74% of the bioactivity of monomeric prolactin. However, a consistent pattern was not observed for all sera. In seven of the sera tested, macroprolactin was considerably less potent than monomeric prolactin (60% plus/minus 20%; mean plus/minus SD). In the remaining three sera the converse was observed with macroprolactin exhibiting equal or slightly increased bioactivity (106% plus/minus 8%).

Our results demonstrate that macroprolactin is bioactive in vitro, though in general it exhibits somewhat reduced bioactivity relative to monomeric prolactin. In vivo, the high molecular mass macroprolactin complex is likely to be confined to the vascular system rendering it bio-unavailable to target tissues. In this context, it is likely that the lack of characteristic clinical signs and symptoms observed in patients harbouring macroprolactin is explained by its bio-unavailibility rather than an intrinsic absence of bioactivity.