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Hyperprolactinemia in Asymptomatic Patients is Related to High Molecular Weight Posttranslational Variants or Glycosylated Forms

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Abstract

Circulating human Prolactin (PRL) exists in different variants related to posttranslational modifications, dimerization or association with other serum proteins. Compared to monomeric prolactin these variants usually have little or no biologic activity and include BigBig (BB PRL), Big (B PRL), and Glycosylated forms (G PRL). The aim of the present study was to assess levels of BB PRL, B PRL, little PRL (L PRL) and G PRL in hyperprolactinemic patients with no menstrual alterations or galactorrhea. L PRL, B PRL, and BB PRL were identified by gel filtration chromatography on Sephadex G-100; G PRL and NG PRL were identified by chromatography on Concanavalin A Sepharose. PRL was measured by IRMA DPC. Eleven women, aged 22–50 yrs, were studied for: breast dysplasia (1), controlled hypothyroidism (3), dysmenorrhea (3), microadenoma follow-up (2), and gynecological control (2). Pituitary MRI was normal in all but one patient, who had a microadenoma discovered by Magnetic Resonance Imaging. Six patients had normal L PRL levels, and their hyper PRL was due to excess BPRL or BB PRL. Five patients had increased L PRL levels, but excess G PRL. Patients harboring molecular PRL variants do not present the symptoms typical of the hyperprolactinemic syndrome. Furthermore in patients with clinically controlled prolactinomas the presence of PRL variants should be ruled out to avoid an unnecessary increase of dopamine agonist dosage.

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References

  1. Sinha YN. Structural variants of prolactin: Occurrence and physiological significance. Endocrine Reviews 1995;16:354–369.

    Google Scholar 

  2. Smith CR, Norman MR. Prolactin and growth hormone: Molecular heterogeneity and measurement in serum. Ann Clin Biochem 1990;27:542–550.

    Google Scholar 

  3. Jackson RD, Wortsman J, Malarkey WB. Characterization of a large molecular weight prolactin in women with idiopathic hyperprolactinemia and normal menses. J Clin Endocrinol Metab 1985;61:268–264.

    Google Scholar 

  4. Bjoro T, Morkrid L, Wergeland R, Turter A, Kvistborg A, Sand T, Torjesen P. Frequency of hyperprolactinemia due to large molecular weight prolactin (150-170 kD PRL). Scan J Clin Lab Invest 1995;55:139–147.

    Google Scholar 

  5. Vallette-Kasic S, Morange Ramos I, Selim A, Gunz G, Morange S, Enjalbert A, Martin MP, Jaquet P, Brue T. Macroprolactinemia revisited:Astudy on 106 patients. J Clin Endocrinol Metab 2002;87:581–588.

    Google Scholar 

  6. Cavaco B, Leite V, Amparo Santos M, Arranhado E, Sobrinho LG. Some forms of big-big prolactin behave as a complex of monomeric prolactin with an Inmunoglobulin G in patients with Macroprolactinemia or Prolactinoma. J Clin Endocrinol Metab 1995;80:2342–2346.

    Google Scholar 

  7. Hattori N, Ishihara T, Ikekubo K, Moridera K, Hino M, Kurahachi H. Autoantibody to human prolactin in patients with idiopatic hyperprolactinemia. J Clin Endocrinol Metab 1992;75:1226–1229.

    Google Scholar 

  8. Miyai K, Ichihara K, Kondo K, Mori S. Asymptomatic hyperprolactinemia and prolactinoma in the general populationmass screening by paired assays of serum prolactin. Clin Endocrinol (Oxford) 1986;25:549–554.

    Google Scholar 

  9. Leite V, Cosby H, Sobrinho LG, Fresnoza A, Amparo Santos MA, Friesen HG. Characterisation of big-big prolactin in patients with hyperprolactinemia. Clin Endocrinol 1992;37:365–372.

    Google Scholar 

  10. Hoffmann T, Penel C, Ronin C. Glycosilation of human prolactin regulates hormone bioactivity and metabolic clearance. J Endocrinol Invest 1993;16:807–816.

    Google Scholar 

  11. Scaglia HE, Forestieri O, Colombani ME, Aquilano DR. La Hiperpprolactinemia Observada en una paciente debido a la variante molecular Big-glicosilada no produjo galactorrea ni alteraciones del ciclo menstrual. RAEM 1998;35:138–143.

    Google Scholar 

  12. Cortelezzi M, Scaglia HE. Determinaci ´on de las variantes Moleculares de PRL por Diferentes m´etodos. Pr´ acticas realizadas por los alumnos del curso de Capacitaci ´on y Especializaci ´on Bioquimica en Endocrinolog´?a Ginecol ´ ogica y Reproductiva. Bolet´?n de la Sociedad Argentina de Endocrinolog´?a Ginecol´ogica y Reproductiva 2000;VII:23–39.

    Google Scholar 

  13. Lewis UJ, Singh RNP, Lewis LJ. Two forms of glycosylated human prolactin have different pigeon crop sac-stimulating activities. Endocrinology 1989;124:1558–1563.

    Google Scholar 

  14. Tanaka T, Shiu RPC, Gout PW, Beer CT, Noble RL, Friesen HG. A new sensitive and specific bioassay for lactogenic hormones: Measurement of prolactin and growth hormone in human serum. J Clin Endocrinol Metab 1980;51:1058.

    Google Scholar 

  15. Carlson HE, Markoff E, Lee DW. On the nature of serum prolactin in two patients with macroprolactinemia. Fertil Steril 1992;58:78–87.

    Google Scholar 

  16. Markoff E, Sigel MB, Lacour N, Seavey BK, Friesen HG, Lewis UJ. Glycosylation selectively alters the biological activity of prolactin. Endocrinology 1988;123:1303–1306.

    Google Scholar 

  17. Whittaker PG, Wilcox T, Lind T. Maintained fertility in a patient with hyperprolactinemia due to a big-big prolactin. J Clin Endocrinol Metab 1981;53:863–866.

    Google Scholar 

  18. Corenblum B. Asymptomatic hyperprolactinemia resulting from macroprolactinemia. Fertil Steril 1990;53:165–167.

    Google Scholar 

  19. Guay AT, Sabharwal P, Varma S, Malarkey WB. Delayed diagnosis of psychological erectile dysfunction because of the presence of macroprolactinemia. J Clin Endocrinol Metab 1996;81:2512–2514.

    Google Scholar 

  20. Fahie-Wilson MN, Soule SG. Macroprolactinemia: Contribution to hyperprolactinemia in a district general hospital and evaluation of a screening test based upon precipitation with polyethylene glycol. Ann Clin Biochem 1997;34:252–258.

    Google Scholar 

  21. Cavaco B, Prazeres S, Santos MA, Sobrinho LG, Leite V. Hyperprolactinemia due to bigbig prolactin is differently detected by commercially available immunoassays. J Endocrinol Invest 1999;22:203–208.

    Google Scholar 

  22. Okuloga AO, Kane JW. Macroprolactinemia: Validation and application of the polyethylene glycol precipitation test and clinical characterization of the condition. Clin Endocrinol (Oxford) 1999;51:119–126.

    Google Scholar 

  23. Hauache OM, Rocha AJ, Maia Jr A, Maciel R, Vieira JG. Screening for macroprolactinemia and pituitary imaging studies. Clin Endocrinol 2002;57:327–331.

    Google Scholar 

  24. Chanson P, Daujat F, Young J, Belluci A, Kujas M, Doyon D, Schaison G. Normal pituitary hypertrophy as a frequent cause of pituitary incidentaloma: A follow-up study. J Clin Endocrinol Metab 2001;86:3009–3015.

    Google Scholar 

  25. Tritos NA, Guay AT, Malarkey WB. Asymptomatic "big" hyperprolactinemia in two men with pituitary adenomas. Case report. Eur J Endocrinol 1998;138:82–85.

    Google Scholar 

  26. Fang VS, Refetoff S. Heterogeneous human prolactin from a giant pituitary tumor in a patient with panhypopituitarism. J Clin Endocrinol Metab 1978;47:780–787.

    Google Scholar 

  27. Guido R, Valenti S, Foppiani L, De Martini D, Cossu M, Giusti M. Prolactin decrease and shift to a normal like isoform profile during treatment with quinagolide in a patient affected by an invasive prolactinoma. J Endocrinol Invest 1997;20:289–293.

    Google Scholar 

  28. Vieira JGH, Tachibana TT, Obara LH, Maciel RMB. Extensive experience and validation of polyethylene glycol precipitation as a screening method for macroprolactinemia. Clin Chem 1998;44:1758–1759.

    Google Scholar 

  29. Leslie H, Courtney CH, Bell PM, Hadden DR, McCance DR, Ellis PK, Sheridan B, Atkinson AB. Laboratory and clinical experience in 55 patients with macroprolactinemia identified by a simple polyethylene glycol precipitation method. J Clin Endocrinol Metab 2001;86:2743–2746.

    Google Scholar 

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Guitelman, M., Colombani-Vidal, M., Zylbersztein, C. et al. Hyperprolactinemia in Asymptomatic Patients is Related to High Molecular Weight Posttranslational Variants or Glycosylated Forms. Pituitary 5, 255–260 (2002). https://doi.org/10.1023/A:1025381917677

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  • DOI: https://doi.org/10.1023/A:1025381917677

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