Heterogeneity of Serum Prolactin Throughout the Menstrual Cycle and Pregnancy in Hyperprolactinemic Women with Normal Ovarian Function*

Abstract

We have demonstrated the selective secretion of high mol wt PRL series (big big PRL) in women with hyperprolactinemia and normal ovarian function. This observation suggests that big big PRL is immunologically similar, but biologically less active, than monomeric or little PRL. In this study we determined the molecular size heterogeneity of immunoreactive PRL in the serum from two ovulatory hyperprolactinemic women (subjects A and B) who had large amounts of serum big big PRL during a menstrual cycle and/or gestation. Serum samples obtained throughout the menstrual cycle (days 6, 10, 14, 17, 23, and 28, taking as day 1 the first day of bleeding) and pregnancy (weeks 7, 9, 11, 15, 20, 25, 30, 34, and 38) were fractionated by gel filtration chromatography. PRL was identified in column eluates by specific RIA. Two additional pregnant women, one with a bromocriptine-treated PRL-secreting adenoma (subject C), and a normal woman (subject D) were studied. Big big PRL was the predominant species throughout the different phases of the menstrual cycle in subject B, comprising 70-80% of the total immunoreactive PRL. Most of the remainder was big PRL, and little PRL was present in only small amounts (6-12%) during the luteal phase. During their pregnancies, the serum PRL in subjects A and B initially was mostly big big PRL, but later in gestation the PRL composition shifted from the high mol wt variants to little PRL. The infant's cord (subject A) and peripheral (subject B) serum at birth contained appreciable quantities of big big and big PRL, respectively. These results indicate that structural changes in PRL occur during pregnancy and the menstrual cycle which are probably influenced by the hormonal environment. In addition, the occurrence of larger mol wt PRL species in the serum of the infant of a hyperprolactinemic mother suggests that the presence of high proportions of big big PRL in the serum is genetically determined.

Clinical relevance of macroprolactin

“…When sera from two pregnant females with macroprolactinaemia were examined at frequent intervals throughout pregnancy, serum PRL was initially primarily in the macroprolactin form 82 . Furthermore, cord blood obtained at birth was shown to contain appreciable quantities of macroprolactin.…”

Gross Variability in the Detection of Prolactin in Sera Containing Big Big Prolactin (Macroprolactin) by Commercial Immunoassays

“…These include a monomer of molecular mass 23 kDa, which accounts for approximately 85% of the PRL present in normal individuals, a 50-kDa species accounting for 10 -15%, and a small but variable amount of a high-molecular-mass form (ϳ150 kDa) termed big big PRL or macroprolactin. In the case of sera from hyperprolactinemic individuals, the relative proportions of such circulating forms can be quite different (3,4). The prevalence of macroprolactin in hyperprolactinemic sera has been reported as 15-26% (5)(6)(7)(8)(9).…”

“…As a consequence, subjects whose hyperprolactinemia can be accounted for by the presence of macroprolactin, i.e. have macroprolactinemia, may not exhibit the classic signs or symptoms of the hyperprolactinemic syndrome such as galactorrhea, menstrual irregularities, or infertility (3,4,17). However, these nonspecific symptoms prompt measurement of PRL.…”

Identification of macroprolactin in a patient with asymptomatic hyperprolactinemia as a stable PRL-IgG complex

“…However, composition and biological significance of macroprolactin ("big,big PRL") are still under debate. In macroprolactinemic patients clinical symptoms commonly associated with hyperprolactinemia -menstrual irregularities (or impotence), reduced fertility, galactorrhea -are often absent (Jackson et al, 1985;Larrea et al, 1989). These observations have led to the concept that big,big PRL has reduced bioactivity compared to monomeric PRL.…”