Large Molecular Size Prolactin with Reduced Receptor Activity in Human Serum: High Proportion in Basal State and Reduction after Thyrotropin-Releasing Hormone*

Abstract

Previous studies of PRL heterogeneity in serum have been chiefly confined to specimens with pathologically or physiologically elevated levels of the hormone. We have examined distribution patterns of PRL after Sephadex chromatography in the sera of eight normal adults before and 15, 60, and 120 min after iv TRH. Column eluates were concentrated by lyophilization and assayed by both RIA and radioreceptor assay (RRA). Lyophilization produced no significant changes in immunological activity of the different fractions. High proportions (mean, 24% range, 12–38%) of immunoreactive material appearing close to the void volume (big big PRL) were noted in all specimens in the resting state. The proportions of big and little (monomer) PRL were 18% and 58%, respectively. The relative proportion of big big PRL declined abruptly 15 min after TRH (mean, 12.9% range, 3–23%), with a corresponding increase in little PRL; there was a restoration of the zero-min pattern by 60–120 min. Receptor assays confirmed this shift in distribution pattern but showed lower percentages for big big and big PRL at all time intervals than did RIAs. RRA:RIA ratios of PRL were: big big, 0.272; big, 0.561; and little, 1.98. These studies indicate that in normal adults in the resting state, a considerable proportion of immunoreactive circulating PRL exists in the big big form, which has low receptor activity; acute stimulation with TRH favors the production of the little form, which exhibits a high ratio of receptor to immunological activity. Big PRL also has reduced receptor activity compared with little PRL.