ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 37 of 45
JMBS 2018, 3(3): 209–213
Medicine. Reviews

The Role of Prolactin in the Development of Mammary Gland Pathology

Kolomiyets O. O. 1,2, Yazykov O. V. 2, Lyndin M. S.1 , Moskalenko R. A. 1

This article presents an overview of prolactin (PRL) participation in the development of mammary gland pathology. Significance of the problem is determined by the general increase in the number of breast cancer. Violation of hormonal regulation is an important factor in the development of breast cancer and tumors of other localizations in the human reproductive system. A significant role in this imbalance is played by PRL. The purpose of the study was to conduct a literature review to determine the role of prolactin in the development of breast cancer. Prolactin is a polypeptide hormone that is synthesized and excreted from the lactotrophic cells of the anterior part of the pituitary gland. Outside the pituitary gland, PRL is encoded by the endometrium, decidual envelope, the lymphocytes, by the central nervous system, mammary gland and the prostate, where it acts as a cytokine. Secretion of PRL is regulated by dopaminergic, adrenergic, cholinergic, and also serotonergic units of the autonomic nervous system. In the mammary gland, PRL exists as a circulating pituitary hormone and in the form of a hormone produced by the epithelium duct. In breast prolactin binds to the cell’s surface of the prolactin receptor (PRL-R). There are six isoforms of PRL-R that determine the effects of prolactin in human tissue. The main effects of PRL in the tissue of mammary gland are mammogenesis, lactogenesis and galactopoietics. Increased level of PRL in biological fluids and body tissues plays an important role in breast pathology. High levels of prolactin hormone are more inherent to young women than menopausal women, because of reducing estrogen exposure and inhibiting lactothorophytic cells. In general, hyperprolactinemia can affect not only the pathology of mammary gland, but also cause abnormalities in the reproductive system, causing anovulatory cycles, amenorrhea, and infertility. Pathological manifestations in breast tissues can be caused not only by the blood prolactin circulating, but also the PRL, which is secreted by own mammary gland tissues, which is one of the factors of carcinogenesis and has great importance in the breast cancer development. PRL increases proliferative activity of the mammary gland cells and affects the regulation of apoptosis. It acts as a pro-oncogen in early neoplastic transformation, progression and forms a resistance to cancer treatment. Besides increased expression of prolactin receptor, it also leads to increased proliferation and invasive tumor growth, and conversely the PRL-R antagonist leads to a decrease clonogenic activity of the cells of breast cancer and potentiated the effect of cytotoxic drugs. Consequently, expression of prolactin receptor may be a marker for the differentiation of epithelial cells of the affected mammary gland. Conclusions. Further investigation of the pathogenetic mechanisms and their effect of PRL expression on the tissue of mammary gland can greatly contribute for the development of new methods of diagnosing and treating breast cancer.

Keywords: breast cancer, prolactin, prolactin receptor expression, hyperprolactinemia

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  1. Andreeva EN, Khamoshin MB, Rudneva OD. Prolaktin i molochnye zhelezy: norma i patologiya. Ginekologiya. 2012; 1: 12–6. [Russian]
  2. Byuleten Natsionalnogo kantser-reyestru № 17 "Rak v Ukrayini [digital resource]. Natsionalniy institut raku. 2014. Available from: [Ukrainian]
  3. Lychkova AE, Puzikov AM. Aktualnye voprosy fiziologii. Prolaktin i serotonin. Vestnik RAMN. 2014; 1: 38–45. [Russian]
  4. Redelman D, Welniak LA, Taub D, Murphy WJ. Neuroendocrine Hormones such as Growth Hormone and Prolactin are Integral Members of the Immunological Cytokine Network. Cell Immunol, 2008; 252 (1-2): 111–21.
  5. Aksamitiene E, Achanta S, Kolch W, Kholodenko BN, Hoek JB, Kiyatkin A. Prolactin-Stimulated Activation of ERK1/2 Mitogen-Activated Protein Kinases is Controlled by PI3-Kinase/Rac/PAK Signaling Pathway in Breast Cancer Cells. Cell Signal. 2011; 23 (11): 1794–805.
  6. Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev. 1998; 19, 225–68.
  7. Mcneilly A. Lactation and the physiology of prolactin secretion. Postgraduate Medical J. 1965; 51: 231–5.
  8. Grattan DR. 60 Years Of Neuroendocrinology: The hypothalamo-prolactin axis. J Endocrinol. 2015; 226 (2): 101–22.
  9. Van Klompenberg MK, Manjarín R, Donovan CE, Trott JF, Hovey RC. Regulation and localization of vascular endothelial growth factor within the mammary glands during the transition from late gestation to lactation. Domest Anim Endocrinol. 2015; 54: 37-47.
  10. Besser G, Parke L, Edwards C, Mcneilly A. Galactorrhoea: successful treatment with reduction of plasma prolactin levels by brom-ergocryptine. British Medical J. 1972; 3 (5828): 669-72.
  11. Contesso G, Ceriani B, Nata F. In vitro hormone induced differentiation of human mammary gland. Fourth International Congress of Endocrinology. Amsterdam: Excerpta Medica, 1972. P. 265.
  12. Gorvin CM. The prolactin receptor: Diverse and emerging roles in pathophysiology. J Clin Transl Endocrinol. 2015; 2 (3), 85–91.
  13. Pałubska S, Adamiak-Godlewska A, Winkler I, Romanek-Piva K, Rechberger T, Gogacz M. Hyperprolactinaemia – a problem in patients from the reproductive period to the menopause. Prz Menopauzalny. 2017; 16 (1): 1–7.
  14. Cutie E, Nieves A, Andino M. Prolactin inhibits the steroidogenesis in midfollicular phase human granulosa cells cultured in a chemically defined medium. Fertil Steril. 1988; 49: 632–7.
  15. Shimon I, Bronstein M, Shapiro J, Tsvetov G, Benbassat C, Barkan A. Women with prolactinomas presented at the postmenopausal period. Endocrine. 2014; 47: 889–94.
  16. Shibli-Rahhal A, Schelechte J. The effects of hyperprolactinemia on bone and fat. Pituitary. 2009; 12: 96–104.
  17. Seriwatanachai D, Krishnamra N, Van Leeuwen JP. Evidence for direct effects of prolactin on human osteoblasts: Inhibition of cell growth and mineralization. J Cell Biochem. 2009; 107: 677–85.
  18. Gill S, Peston D, Vonderhaar B, Shousha S. Expression of prolactin receptors in normal, benign, and malignant breast tissue: an immunohistological study. J Clin Pathol. 2001; 54: 956–60.
  19. Michel E, Feldmann KS. Expression of prolactin receptors in normal canine mammary tissue, canine mammary adenomas and mammary adenocarcinomas. BMC Vet Res. 2012; 8: 72.
  20. Hachim IY, Hachim MY, Lopez VM, Lebrun JJ, Ali S. Prolactin Receptor Expression is an Independent Favorable Prognostic Marker in Human Breast Cancer. Horm Cancer. 2014; 5 (1): 42-50.
  21. Nouhi Z, Chughtai N, Hartley S, Cocolakis E, Lebrun JJ, Ali S. Defining the role of prolactin as an invasion suppressor hormone in breast cancer cells. Cancer Res. 2006; 66: 1824–32.
  22. Howell SJ, Anderson E, Hunter T, Farnie G, Clarke RB. Prolactin receptor antagonism reduces the clonogenic capacity of breast cancer cells and potentiates doxorubicin and paclitaxel cytotoxicity. Breast Cancer Res. 2008; 10: 68.
  23. Plotnikov A, Varghese B, Tran TH, Liu C, Rui H, Fuchs SY. Impaired turnover of prolactin receptor contributes to transformation of human breast cells. Cancer Res. 2009; 69: 3165–72.
  24. Chen WY, Ramamoorthy P, Chen N, Sticca R, Wagner TE. A human prolactin antagonist, hPRL-G129R, inhibits breast cancer cell proliferation through induction of apoptosis. Clin Cancer Res. 1999; 5: 3583–93.
  25. Perks CM, Keith AJ, Goodhew KL, Savage PB, Winters ZE, Holly JM. Prolactin acts as a potent survival factor for human breast cancer cell lines. Br J Cancer. 2004; 91: 305–11.
  26. Dong J, Tsai-Morris C, Dufau M. A novel estradiol/estrogen receptor a-dependent transcriptional mechanism controls expression of the human prolactin receptor. J Biol Chem. 2006; 281: 18825–36.