Size Heterogeneity of Human Prolactin in Plasma and Pituitary Extracts

Abstract

Two discrete components of circulating human prolactin have been identified by immunoassay after gel filtration of Sephadex G-100 in all plasma samples so far examined. The major peak, termed “little” prolactin, eluted coincident with purified 131I-prolactin. The less retarded second peak, termed “big” prolactin, emerged between human serum albumin and ovalbumin. “Big” and “little” prolactin fractions were indistinguishable immunologically when assayed at multiple dilutions. “Big” prolactin constituted 8–20% of the total immunoreactivity in plasma samples from normal subjects, patients with chromophobe adenomas, and idiopathic galactorrhea. Neither TRH stimulation nor l-dopa suppression produced major changes in the plasma ratios of “big” to “little” prolactin, which were similar in normals and tumor patients. The highest amounts of “big” prolactin (range 16–31%) were seen in plasmas from pregnant subjects. Both components also appear to be present in pituitary extracts and pituitary culture media. On rechromatography, both components maintained characteristic elution patterns with no shift in their respective positions. Freezing and thawing or prolonged storage caused considerable conversion of the “big” to “little” component (25–38%). These procedures also induced some formation of a third immunoreactive component, eluting close to the void volume, considered to represent a high molecular weight aggregate. Conversion of the “little” to “big” component was not observed in any circumstances, including incubation of “little” prolactin with hypopituitary plasma. These results suggest that “big” prolactin is produced and secreted by the pituitary gland, and that it represents “little” prolactin loosely associated with another component of as yet undetermined nature.