Detailed Assessment of Big Big Prolactin in Women with Hyperprolactinemia and Normal Ovarian Function

Abstract

Six women with elevated circulating levels of big big PRL (BBPRL) and apparently normal ovarian function were variously studied through a menstrual cycle and menstruation, through pregnancy and suckling, and during stimulation tests with TRH and suppression with bromocriptine. No significant changes in monomeric PRL were demonstrated during the menstrual cycle, but all subjects showed a small and significant rise in BBPRL during the preovulatory phase. High PRL levels were present in day 1 menstrual plasma, but BBPRL was only present in low concentrations. All subjects (n = 5) demonstrated a rise in both PRL and BBPRL during pregnancy, with a consistent tendency for PRL to increase to a proportionately greater extent than BBPRL. One subject exhibited a rise in PRL (by 93%), but not BBPRL, 30 min after suckling. TRH caused a brisk rise in PRL (by 363 +/- 116%) but only a sluggish rise in BBPRL (by 17.5 +/- 7.4%; n = 3). Bromocriptine rapidly suppressed PRL (by 81.8 +/- 34.4%), but only slowly suppressed BBPRL (by 21.0 +/- 8.7% after 6 h; n = 3). Plasma binding studies did not demonstrate any evidence of a circulating specific PRL-binding protein. These data indicate that plasma concentrations of BBPRL may vary under the influence of a number of factors, but are much less sensitive to TRH stimulation, bromocriptine suppression, pregnancy, and suckling than PRL. The occurrence of BBPRL does not seem to be due to a specific circulating binding protein.

Clinical and biological characterization of macroprolactinemia with and without prolactin-IgG complexes

“…Neither serum total PRL immunoactivity nor free PRL values were found to be higher in these symptomatic patients. We cannot exclude, however, that because of a low stability of the high molecular mass PRL complexes, monomeric PRL levels are fluctuating and reach high levels, leading to clinical symptoms in some conditions (13,21). A consistent tendency for monomeric PRL to increase faster than the high molecular mass PRL has been observed in macroprolactinemic women during pregnancy (21).…”

“…A reduced biological activity of macroprolactin (compared with monomeric PRL) has been suggested as the reason for lack of symptoms in macroprolactinemic patients (11,21,23). On the other hand, some studies, often based on single-case reports, found that serum containing high molecular mass PRL exhibited lower, higher or similar biological activity compared with serum with monomeric PRL (11,15,27,28).…”

Macroprolactinaemia: Contribution to Hyperprolactinaemia in a District General Hospital and Evaluation of a Screening Test Based on Precipitation with Polyethylene Glycol

“…Soong et al 14 (1982) may remain asymptomatic despite marked macroprolactinacmia.V' H. 12 The notion that a high molecular weight prolactin-immuno-globulin complex may have a reduced capacity to cross vascular endothelium and thus limited bioactivity is attractive? and finds some support from our clinical data (Table I).…”

Serum Total Prolactin and Monomeric Prolactin Reference Intervals Determined by Precipitation with Polyethylene Glycol: Evaluation and Validation on Common ImmunoAssay Platforms

“…Monomeric prolactin (M r 23 000) is the most common form of circulating prolactin in healthy in-dividuals and most patients with true hyperprolactinemia, but forms with higher molecular mass are also present, such as big prolactin (M r 60 000) and big-big prolactin or macroprolactin [M r 150 000) (4,8,20,21 )]. Macroprolactin is reported to be the cause of hyperprolactinemia in up to 26% of cases, with percentages varying depending on the assay used (3,22 ).…”