The frequency of macroprolactinemia related to the presence of anti-PRL aut
oantibodies in the serum of 209 healthy women at different stages of pregna
ncy was studied. Measurements were taken of serum PRL concentrations before
and after chromatographic separation (gel filtration and affinity with pro
teins A and G) and extraction of free PRL with polyethylene glycol(PEG). Se
ra from 8 of the 209 women (3.8%) were found to have a significantly high p
roportion of precipitated PRL by PEG (macroprolactinemia); in these patient
s, gel filtration showed that a substantial amount of big big PRL (molecula
r mass >100 kDa) was present (19.0-78.2% vs. 3.8-4.9%, P = 0.009 in normal
pregnant women with a normal proportion of precipitated PRL by PEG). The pr
esence of macroprolactinemia was attributable to anti-PRL autoantibodies in
5 of the 8 women. Comparison of serum levels of direct and free PRL betwee
n women with macroprolactinemia related to anti-PRL autoantibodies and wome
n without macroprolactinemia showed significant differences (direct PRL: 27
0.2 +/- 86.9 vs. 203.4 +/- 69.0 mug/L, P = 0.04; and free PRL: 107.0 +/- 75
.9 vs. 173.3 +/- 67.6 mug/L, P = 0.002). On the other hand, there was no di
fference between women with macroprolactinemia not related to anti-PRL auto
antibodies and women with macroprolactinemia caused by anti-PRL autoantibod
ies, nor was there a difference between women with macroprolactinemia not r
elated to anti-PRL autoantibodies and women without macroprolactinemia. The
re was a positive correlation between titers of the anti-PRL autoantibody a
nd serum PRL levels (r = 0.82, P = 0.09). The presence of the anti-PRL auto
antibody had no relation to the patient's age, stage of gestation, or numbe
r of previous pregnancies. We concluded that the frequency of macroprolacti
nemia was 3.8% among healthy, pregnant women, which was caused by a anti-PR
L autoantibodies in 62.5% of the cases. The autoantibodies were found in th
e bloodstream, forming a PRL-IgG complex, in accordance with the following
observations: 1) immunoreactive PRL on gel filtration was eluted in the fra
ctions corresponding to the molecular mass of IgG (150 kDa); 2) a significa
ntly high proportion of immunoreactive PRL was retained on an affinity gel
for IgG (proteins A and G); and 3) a significantly high proportion of serum
PRL bound to IgG was precipitated by protein A. There was a positive corre
lation between titers of anti-PRL autoantibodies and serum PRL levels. Seru
m levels of total PRL were higher, and serum levels of free PRL were lower,
in pregnant women with anti-PRL autoantibodies than in pregnant women with
out macroprolactinemia.