Polymers of Prolactin and Their Clinical Significance

Fraser, Ian S.; Zhuang, Guobing

doi:10.1097/00006254-199008000-00003

Cited by 14 publications

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“…Physiological levels of PRL are higher during pregnancy and lactation than otherwise and mean serum levels are higher in women than in men 26,27 . In addition to monomeric PRL, which accounts for approximately 85% of the total circulating PRL in the majority of normal subjects and in those patients with hyperprolactinaemia, other molecular weight variants of PRL can be demonstrated in serum 28,29 . Big PRL, which has a molecular mass in the 50 kDa range and is thought to be a covalently bound dimer of PRL, accounts for approximately 10–15%.…”

Section: Prolactin and Macroprolactinmentioning

confidence: 99%

Clinical relevance of macroprolactin

Gibney

Smith

McKenna

2005

Clinical Endocrinology

131

108

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The anterior pituitary hormone PRL was identified in animal species as early as 1933 1 but only purified in humans in 1972. 2 Since then, the clinical syndrome of hyperprolactinaemia has been characterized extensively, the predominant symptoms being galactorrhoea, oligomenorrhoea or amenorrhoea and infertility in women and reduced libido, impotence and galactorrhoea in men. [3][4][5][6][7][8] Hyperprolactinaemia has an estimated prevalence of 15% in women with secondary amenorrhoea, 9,10 a condition that affects at least 3% of women of reproductive age. 11Pathological hyperprolactinaemia results from a lactotroph adenoma, conditions that increase TRH, such as hypothyroidism, conditions that decrease dopamine action at the lactotroph cell, such as hypothalamic or pituitary tumours, drugs such as dopamine D2 receptor antagonists, or conditions in which reduced clearance of PRL occurs, such as renal failure. By contrast, macroprolactinaemia, the presence of elevated levels of PRL of high molecular mass with little, if any, bioactivity, remains a largely under-recognized phenomenon and is not considered in the differential diagnosis of hyperprolactinaemia in current comprehensive endocrinology texts. 3,4,6 Recent studies have indicated that macroprolactinaemia accounts for up to 26% of biochemical hyperprolactinaemia depending on the immunoassay in use, [12][13][14][15][16][17][18] and thus macroprolactinaemia represents a common diagnostic pitfall, which is responsible for frequent misdiagnosis and mismanagement of hyperprolactinaemic patients. 19-23 Prolactin and macroprolactinProlactin, a globular protein consisting of 199 amino acids with three intramolecular disulfide bonds, is synthesized as a prehormone with a molecular weight of 26 kDa. 24 When the prehormone is proteolytically cleaved, the resulting mature polypeptide has a molecular weight of 23 kDa, and this monomeric form accounts for the majority of total PRL in the serum of normal subjects and most patients with hyperprolactinaemia. Prolactin is secreted episodically by the anterior pituitary and is primarily under tonic inhibitory control of the hypothalamus. 25 Physiological levels of PRL are higher during pregnancy and lactation than otherwise and mean serum levels are higher in women than in men. 26,27 In addition to monomeric PRL, which accounts for approximately 85% of the total circulating PRL in the majority of normal subjects and in those patients with hyperprolactinaemia, other molecular weight variants of PRL can be demonstrated in serum. 28,29 Big PRL, which has a molecular mass in the 50 kDa range and is thought to be a covalently bound dimer of PRL, accounts for approximately 10-15%. Big big PRL, or macroprolactin, which has a molecular mass of more than 150 kDa, usually contributes a small, though variable amount to circulating levels. 28,30Moreover, post-translational modification of pituitary PRL generates a variety of additional species, including glycosylated and phosphorylated variants, together with 14, 16 and 22 kDa proteolysed fo...

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Section: Prolactin and Macroprolactinmentioning

confidence: 99%

Clinical relevance of macroprolactin

Gibney

Smith

McKenna

2005

Clinical Endocrinology

131

108

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show abstract

“…In addition, there are two other isoforms with a higher molecular mass, big PRL (45-50 kDa), and big big PRL (Ͼ100 kDa). [16][17][18] These isoforms can be attributable to post-translation modifications (aggregates of monomeric PRL, and PRL bound to binding proteins). These modifications of PRL may affect their biological properties differently from immunoreactivity.…”

Section: Introductionmentioning

confidence: 99%

Anti-prolactin autoantibodies in pregnant women with systemic lupus erythematosus: maternal and fetal outcome

Leaños‐Miranda

Cárdenas-Mondragón

Ulloa‐Aguirre

et al. 2007

Lupus

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The aim of this study was to determine in pregnant women with systemic lupus erythematosus (SLE) the frequency of anti-prolactin autoantibodies and to compare the outcome of pregnancy in SLE women with and without anti-prolactin autoantibodies. Ninety-nine consecutive SLE pregnant women and 151 healthy pregnant women were studied prospectively. Patients with or without anti-prolactin autoantibodies were identified by gel filtration chromatography and affinity chromatography for IgG. Serum total and free prolactin (PRL) levels and molecular heterogeneity of PRL at each trimester of pregnancy were determined. The frequency of anti-PRL autoantibodies in SLE pregnant women was 13.1%. Serum total PRL levels were significantly higher in women with anti-PRL autoantibodies compared with SLE women without anti-PRL autoantibodies and in healthy pregnant women; and serum free PRL levels were lower in the third trimester in women with anti-PRL autoantibodies than in healthy pregnant women. In contrast, serum total and free PRL levels were significantly lower in the second and third trimester in SLE pregnant women without anti-PRL autoantibodies compared with healthy pregnant women. All adverse outcomes of pregnancy studied were more frequent in SLE women without anti-PRL autoantibodies than anti-PRL autoantibody-positive SLE women. Moreover, both maternal and fetal main complications were significantly higher in SLE women without anti-PRL autoantibodies than anti-PRL autoantibody-positive SLE women (P

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“…The major circulating isoform of PRL is a 23 kDa single polypeptide chain (monomeric PRL), which comprises up to 80% of the total PRL in serum from normal subjects and the majority of patients with hyperprolactinemia (HPRL). In addition, there are two other PRL isoforms that display higher molecular weights, referred to as big PRL (45–50 kDa) and big big PRL (>100 kDa) and also known as macroprolactin [1]. The presence of these isoforms has been attributed to formation of aggregates of monomeric PRL with different glycosylation degrees and binding of PRL to serum protein in circulation, mainly to anti-PRL autoantibody of IgG isotype [2–5].…”

Section: Introductionmentioning

confidence: 99%

Frequency of Macroprolactinemia in Hyperprolactinemic Women Presenting with Menstrual Irregularities, Galactorrhea, and/or Infertility: Etiology and Clinical Manifestations

Leaños‐Miranda

Ramírez-Valenzuela²,

Campos-Galicia³

et al. 2013

International Journal of Endocrinology

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Aim. To determine the frequency of macroprolactinemia, its etiology, and the clinical manifestations in patients with hyperprolactinemia presenting with menstrual irregularities, galactorrhea, and/or infertility who were attended by the gynecology-endocrinology service. Methods. In a cross-sectional study, 326 hyperprolactinemic women were tested for serum prolactin (PRL) concentrations before and after chromatographic separation (gel filtration and affinity with protein G) and extraction of free PRL with polyethylene glycol (PEG). Results. Sera from 57 patients (17.5%) were found to have macroprolactinemia. The presence of macroprolactinemia was attributable to anti-PRL autoantibodies in 54 (94.7%) patients. The median serum PRL levels were similar in patients with or without macroprolactinemia (42.0 versus 38.1 ng/mL). In contrast, patients with macroprolactinemia had lower serum-free PRL levels (median 9.2 versus 31.7 ng/mL, P < 0.001). Patients without macroprolactinemia had a higher frequency of galactorrhea and abnormal pituitary imagine findings (P < 0.002). Conclusions. We can conclude that macroprolactinemia should be considered as a benign variant, and it must be ruled out in women presenting with menstrual irregularities, galactorrhea, and/or infertility in order to investigate other causes different than hyperprolactinemia. Serum PRL precipitated with PEG is a convenient and simple procedure to screen for the presence of macroprolactinemia.

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Polymers of Prolactin and Their Clinical Significance

Cited by 14 publications

References 0 publications

Clinical relevance of macroprolactin

Clinical relevance of macroprolactin

Anti-prolactin autoantibodies in pregnant women with systemic lupus erythematosus: maternal and fetal outcome

Frequency of Macroprolactinemia in Hyperprolactinemic Women Presenting with Menstrual Irregularities, Galactorrhea, and/or Infertility: Etiology and Clinical Manifestations

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