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Prolactin and human weight disturbances: A puzzling and neglected association

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Abstract

Weight gain at the outset of prolactinomas in many women is well documented. Yet, this symptom is absent from the clinical descriptions of the disease in textbooks and reviews. This omission is almost certainly due to the absence of a physiological explanation for the phenomenon, as prolactin is not a recognized fat promoting hormone. In this review we present the clinical evidence for a relationship between prolactin and fat accumulation and address some possible mechanisms involved. We put forward the hypothesis that prolactin is a component of a neuroendocrine program – maternal subroutine – aimed at optimizing the care of the young through the production of milk, promotion of maternal behavior and increase in the metabolic efficiency of the mother. These adaptations can enable her to face the extraordinary metabolic expenses of pregnancy and nursing, especially during times of suboptimal environmental conditions. We emphasize the uniqueness of prolactin in that it is a hormone that is tonically inhibited and which has its major effects on the regulation of an inter-individual (the mother – offspring dyad), rather than an intra-individual, system. This approach opens a window to consider the possibility of external events as regulators of this system. It also allows addressing a variety of hitherto unexplained findings reported in the literature. Examples include: association of prolactinomas with paternal deprivation and with stressful life events; pseudocyesis; acute life event-driven episodes of galactorrhea; episodes of rapid weight gain following a life event; prolactin surges (without associated cortisol surges) following some psychological stresses.

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References

  1. Forbes AP, Henneman PH, Griswold GC, Albright F. Syndrome characterized by galactorrhea, amenorrhea and low urinary FSH: comparison with acromegaly and normal lactation. J Clin Endocrinol Metab. 1954;14:265–71.

    Article  CAS  PubMed  Google Scholar 

  2. Shibli-Rahhal A, Schlechte J. The effects of hyperprolactinemia on bone and fat. Pituitary. 2009;12:96–104.

    Article  CAS  PubMed  Google Scholar 

  3. Nunes MC, Sobrinho LG, Calhaz-Jorge C, Santos MA, Mauricio JC, Sousa MF. Psychosomatic factors in patients with hyperprolactinemia and/or galactorrhea. Obstet Gynecol. 1980;55:591–5.

    CAS  PubMed  Google Scholar 

  4. Gould BK, Randall RV, Kempers RD, Ryan RJ. Galactorrhoea. Springfield. Ill: CC Thomas; 1974.

  5. Galluzzi F, Salti R, Stagi S, La Cauza F, Chiarelli F. Reversible weight gain and prolactin levels -long-term follow-up in childhood. Journal Ped Endocrinol Metabol. 2005;18:921–4.

    Article  CAS  Google Scholar 

  6. Creemers LB, Zelissen PM, van’t Verlaat JW, Koppeschaar HP. Prolactinoma and body weight: a retrospective study. Acta Endocrinol. 1991;125:392–6.

    Article  CAS  Google Scholar 

  7. Greenman Y, Tordjman K, Stern N. Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels. Clin Endocrinol. 1998;48:547–53.

    Article  CAS  Google Scholar 

  8. Colao A, Sarno AD, Cappabianca P, Briganti F, Pivonello R, Di Somma C, et al. Gender differences in the prevalence, clinical features and response to cabergoline in hyperprolactinemia. Eur J Endocrinol. 2003;148:325–31.

    Article  CAS  PubMed  Google Scholar 

  9. Wallace RB, Sherman BM, Bean JA. Clinical and biological antecedents of the amenorrhea/hyperprolactinemia syndrome: a case control study. Fertil Steril. 1985;43:726–32.

    Article  CAS  PubMed  Google Scholar 

  10. Schmid C, Goede DL, Hauser RS, Brändle M. Increased prevalence of high body mass index in patients presenting with pituitary tumours: severe obesity in patients with macroprolactinoma. Swiss Med Wkly. 2006;136:254–8.

    PubMed  Google Scholar 

  11. Cohen LM, Greenberg DB, Murray GB. Neuropsychiatric presentation of men with pituitary tumors (the “four as”). Psychosomatics. 1984;25:925–8.

    Article  CAS  PubMed  Google Scholar 

  12. Naliato ECO, Violante AHD, Gaccione M, Caldas D, Lamounier Filho A, Loureiro CR, et al. Body fat in men with prolactinoma. J Endocrinol Investig. 2008;31:985–90.

    Article  CAS  Google Scholar 

  13. Doknic M, Pekic S, Zarkovic M, et al. Dopaminergic tone and obesity: an insight from prolactinomas treated with bromocriptine. Eur J Endocrinol. 2002;147:77–84.

    Article  CAS  PubMed  Google Scholar 

  14. Pala NA, Misgar LBARA, RA RDA. Metabolic abnormalities in patients with prolactinoma: response to treatment with cabergoline. Diabetol Metab Syndr. 2015;7:99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Serri O, Li L, Mamputu JC, Beauchamp MC, Maingrette F, Renier G. The influences of hyperprolactinemia and obesity on cardiovascular risk markers: effects of cabergoline therapy. Clin Endocrinol 2006;64:366–70.

  16. Bronstein, M.D. Disorders of prolactin secretion and prolactinomas. in Jameson, J. L. and L. J. DeGroot editors, Endocrinology: Adult and Pediatric. Saunders, Philadelphia, PA. 2016. vol. 1. pp. 333–57.

  17. Matsuda M, Imaoka T, Vomachka AJ, Gudelsky GA, Hou Z, Mistry M, et al. Serotonin regulates mammary gland development via an autocrine-paracrine loop. Dev Cell. 2004;6:193–203.

    Article  CAS  PubMed  Google Scholar 

  18. Stull MA, Pai V, Vomachka AJ, Marshall AM, Jacob GA, Horseman ND. Mammary gland homeostasis employs serotonergic regulation of epithelial tight junctions. Proc Natl Acad Sci U S A. 2007;104:16708–13.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Hernandez LL, Gregerson KA, Horseman ND. Mammary gland serotonin regulates parathyroid hormone-related peptide and other bone-related signals. Am J Physiol Endocrinol Metab. 2012;302:E1009–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Horseman ND, Hernandez LL. New concepts of breast cell communication to bone. Trends Endocrinol Metabol. 2014;25:34–41.

    Article  CAS  Google Scholar 

  21. Kovacs CS, Chik CL. Hyperprolactinemia caused by lactation and pituitary adenomas is associated with altered serum calcium phosphate parathyroid hormone (PTH) and PTH-related peptide levels. J Clin Endocrinol Metab. 1995;80:3036–42.

    CAS  PubMed  Google Scholar 

  22. Stiegler C, Leb G, Kleinert R, Warnkross H, Ramschak-Schwarzer S, Lipp R, et al. Plasma levels of parathyroid hormone-related peptide are elevated in hyperprolactinemia and correlated to bone density status. J Bone Mineral Res. 1995;10:751–9.

    Article  CAS  Google Scholar 

  23. Kim H, Toyofuku Y, Lynn FC, Chak E, Uchida T, Mizukami H, et al. Serotonin regulates pancreatic beta cell mass during pregnancy. Nature Med. 2010;16:804–8.

    Article  CAS  PubMed  Google Scholar 

  24. Baeyens L, Hindi S, Sorenson RL, German MS. β-Cell adaptation in pregnancy. Diabetes, Obesity and Metabol. 2016;18:63–70.

    Article  CAS  Google Scholar 

  25. Sobrinho LG. Neuropsychiatry of prolactin: causes and effects. Ballière's. Clin Endocrinol Metab. 1991;5:119–41.

    CAS  Google Scholar 

  26. Del Pizzo J, Posey-Bahar L, Jimenez R. Pseudocyesis in a teenager with bipolar disorder. Clin Pediatr (Phila). 2011;50:169–71.

    Article  Google Scholar 

  27. Tarin JJ, Hermenegildo C, García-Pérez MA, Cano A. Endocrinology and physiology of pseudocyesis. Reprod Biol Endocrinol. 2013;11:39.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Zarate A, Canales ES, Soria J, Jacobs LS, Daughaday WH, Kastin AJ, et al. Gonadotropin and prolactin secretion in human pseudocyesis. Annales d’Endocrinologe (Paris). 1974;35:445–50.

    CAS  Google Scholar 

  29. Yen SSC, Rebar RW, Quesenberry W. Pituitary function in pseudocyesis. J Clin Endocrinol Metab. 1976;43:132–6.

    Article  CAS  PubMed  Google Scholar 

  30. Osotimehin BO, Ladipo OA, Adejuwon CA. Otolorin EO (1981) pituitary and placental hormone levels in pseudocyesis. Int J Gynaecol Obstet. 1981;19:399–402.

    Article  CAS  PubMed  Google Scholar 

  31. Tulandi T, McInnes RA, Lal S. Altered pituitary hormone secretion in patients with pseudocyesis. Fertil Steril. 1983;40:637–41.

    Article  CAS  PubMed  Google Scholar 

  32. Devane GW, Vera MI, Buhl WC, Kalra PS. Opioid peptides in pseudocyesis. Obstet Gynecol. 1985;65:183–8.

    CAS  PubMed  Google Scholar 

  33. Starkman MN, Marshall JC, La Ferla J, Kelch RP. Pseudocyesis: psychologic and neuroendocrine interrelationships. Psychosom Med. 1985;47:46–57.

    Article  CAS  PubMed  Google Scholar 

  34. Forsbach G, Güitron A, Munoz M, Bustos H. Pituitary function in human pseudocyesis. J Endocrinol Investig. 1987;10:39–43.

    Article  CAS  Google Scholar 

  35. Bray MA, Muneyyirci-Delale O, Kofinas GD, Reyes FI. Circadian, ultradian and episodic gonadotropin and prolactin secretion in human pseudocyesis. Acta Endocrinol. 1991;124:501–9.

    Article  CAS  Google Scholar 

  36. Padayachi T, Ashe R, Moodley J, Jialal I. Pituitary function tests in black patients with pseudocyesis. S Afr Med J. 1991;79:24–6.

    CAS  PubMed  Google Scholar 

  37. Copinschi G, De Laet MH, Brion JP, Leclerc R, L’Hermite M, Robyn C, et al. Simultaneous study of cortisol, growth hormone and prolactin nyctohemeral variations in normal and obese subjects influence of prolonged fasting in obesity. Clin Endocrinol. 1978;9:15–26.

    Article  CAS  Google Scholar 

  38. Kok P, Roelfsma F, Frőlich M, Meinders AE, Pijl H. 2004. Prolactin release is enhanced in proportion to excess visceral fat in obese women. J Clin Endocrinol Metab. 2004;89:4445–9.

    Article  CAS  PubMed  Google Scholar 

  39. Wang DY, de Stavola BL, Bulbrook RD, Allen DS, Kwa HG, Verstraeten AA, et al. The relationship between blood prolactin levels and risk of breast cancer in premenopausal women. Eur J Cancer Clin Oncol. 1987;23:1541–8.

    Article  CAS  PubMed  Google Scholar 

  40. Kok P, Roelfsema F, Langendonk JG, de Wit CC, Frőlich M, Burggraaf J, et al. Am J Physiol Endocrinol Metab. 2006;90:E218–24.

    Article  CAS  Google Scholar 

  41. Ben-Jonathan N, Hugo E. Prolactin (PRL) in adipose tissue: regulation and functions. Adv Exp Med Biol. 2015;846:1–35.

    Article  CAS  PubMed  Google Scholar 

  42. Ferreira MF, Sobrinho LG, Pires JS, Silva MES, Santos MA, Sousa MFF. Endocrine and psychological evaluation of women with recent weight gain. Psychoneuroendocrinology. 1995;20:53–63.

    Article  CAS  PubMed  Google Scholar 

  43. Paykel ES. Methodological aspects of life events research. Adv Psychosomatic Med. 1987;17:13–29.

    Article  CAS  Google Scholar 

  44. Sobrinho L. The psychosomatic interface: hyperprolactinemia. In: Horseman ND, editor. Prolactin. Boston: Kluwer Academic Publishers; 2001.

    Google Scholar 

  45. Baptista T, La Cruz A, Meza T, Contreras Q, Delgado C, Mejìas MA, et al. Antipsychotic drugs and obesity: is prolactin involved? Can J Psychiatr. 2001;46:829–34.

    Article  CAS  Google Scholar 

  46. Yang F, Chen L, Fang X, Zheng K, Zhu C, Xu C, et al. Influence of olanzapine on serum prolactin levels and BMI in female patients with schizophrenia. Neuropsychiatr Dis Treat. 2018;14:3373–9.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Neovius M, Eberhard J, Lindström E, Levander S. Weight development in patients treated with risperidone: a 5-year naturalistic study. Acta Psychiatr Scand. 2007;115:277–85.

    Article  CAS  PubMed  Google Scholar 

  48. Baptista T1, Parada M. Hernandez LLong term administration of some antipsychotic drugs increases body weight and feeding in rats. Are D2 dopamine receptors involved? Pharmacol Biochem Behav. 1987;27:399–405.

    Article  CAS  PubMed  Google Scholar 

  49. Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, et al. Comparative efficacy and toler-ability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382:951–62.

    Article  CAS  PubMed  Google Scholar 

  50. Lord CC, Wyler SC, Wan R, Castorena CM, Ahmed N, Mathew D, et al. The atypical antipsychotic olanzapine causes weight gain by targeting serotonin receptor 2C. J Clin Invest. 2017;127:3402–6.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Baptista T, Contreras Q, Teneud L, Albornoz MA, Acosta A, Páez X, et al. Mechanism of the neuroleptic-induced obesity in female rats. Prog Neuro-Psychopharmacol Biol Psychiatry. 1998;22:187–9.

    Article  CAS  Google Scholar 

  52. Kopchick, J.J, G.A. Martos-Moreno, M. Korbonits, B. D. Gaylinn, R. Nass, and M. O. Thorner.. Regulation of Growth Hormone and Actions (Secretagogues). in Jameson, J. L. and L. J. DeGroot editors, "Endocrinology: Adult and Pediatric" Saunders, Philadelphia, PA. 2016. vol. 1. pp. 412–53.

  53. Wang, S., J. Wu, N. Wang, L. Zeng and Y. Wu 2017 The role of growth hormone receptor in ß cell function. Growth Hormon IGF Res 56:30–35.

  54. Daimon M, Kamba A, Murakami H, Mizushiri S, Osonoi S, Yamaichi M, et al. Association between serum prolactin levels and insulin resistance in non-diabetic men. PLoS One. 2017;12:e0175204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Illingworth PJ, Jung RT, Howie PW, Leslie P, Isles TE. Diminution of energy expenditure during lactation. Brit Med J. 1986;292:437–41.

    Article  CAS  Google Scholar 

  56. Lunn PG, Austin S, Prentice AM, Whitehead RG. Influence of maternal diet on plasma prolactin levels during lactation. Lancet. 1980;1:623–5.

    Article  CAS  PubMed  Google Scholar 

  57. Christensen HR, Murawsky MK, Horseman ND, Willson TA, Gregerson KA. Completely humanizing prolactin rescues infertility in prolactin knockout mice and leads to human prolactin expression in extrapituitary mouse tissues. Endocrinology. 2013;154:4777–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Marano RJ, Ben-Jonathan N. Minireview: Extrapituitary prolactin: an update on the distribution, regulation, and functions. Mol Endocrinol. 2014;28(5):622–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Nagaishi VS, Cardinali LI, Zampieri TT, Furigo IC, Metzger M, Donato J Jr. Possible crosstalk between leptin and prolactin during pregnancy. Neuroscience. 2014;259:71–83.

    Article  CAS  PubMed  Google Scholar 

  60. Jürgensen O, Bardé B. Psychodynamic findings in women with elevated prolactin. In the Yooung Woman. Eds. Dennerstein L, De Senarclens M. Excerpta Médica, International Congress Series, 618, Amsterdam-Oxford–Princeton. 1983, pp 138–148.

  61. Assies J, Vingerhoets AJ, Poppelaars K. (1992) psychosocial aspects of hyperprolactinemia. Psychoneuroendocrinology. 1992;17:673–9.

    Article  CAS  PubMed  Google Scholar 

  62. Rojas LM, Sthory I, Canales ES, Zárate A. Factores psicogénicos en el síndroma de amenorrea-galactorrea. Ginecol Obstet Mex. 1981;49:291–5.

    CAS  PubMed  Google Scholar 

  63. Sobrinho LG, Duarte JS, Paiva I, Gomes L, Vicente V, Aguiar P. Paternal deprivation prior to adolescence and vulnerability to pituitary adenomas. Pituitary. 2012;15:251–7.

    Article  CAS  PubMed  Google Scholar 

  64. Sonino N, Navarrini C, Ruini C, Fallo F, Boscaro M, Fava GA. Life events in the pathogenesis of hyperprolactinemia. European J Endocrinol. 2004;151:61–5.

    Article  CAS  Google Scholar 

  65. Ma W, Ikeda H, Yoshimoto T. Clinicopathologic study of 123 cases of prolactin-secreting pituitary adenomas with special reference to multihormone production and clonality of the adenomas. Cancer. 2002;95:258–66.

    Article  PubMed  Google Scholar 

  66. Burrow GN, Wortzman G, Rewcastle RB, Holgate RC, Kovacs K. Microadenomas of the pituitary and abnormal sellar tomograms in an unselected autopsy series. N Engl J Med. 1981;304:156:8.

    Article  PubMed  Google Scholar 

  67. Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, et al. The prevalence of pituitary adenomas: a systematic review. Cancer. 2004;101:613–9.

    Article  PubMed  Google Scholar 

  68. Buurman H, Saeger W. Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data. Eur J Endocrinol. 2006;154:753–8.

    Article  CAS  PubMed  Google Scholar 

  69. Kovacs K, Stefaneanu L, Horvath E, Buchfelder M, Fahlbusch R, Althoff PH, et al. Pituitary Corticotroph adenoma in a woman with long-standing Addison's disease: a histologic, Immunocytochemical, Electron microscopic, and in situ hybridization study. Endocr Pathol. 1996;7:91–7.

    Article  PubMed  Google Scholar 

  70. Kleinberg D. Pituitary tumors and failure of endocrine target organs. Arch Intern Med. 1979;139:969–70.

    Article  CAS  PubMed  Google Scholar 

  71. Nicolis G, Shimshi M, Allen C, Halmi NS, Kourides IA. Gonadotropin-producing pituitary adenoma in a man with long-standing primary hypogonadism. J Clin Endocrinol Metab. 1988;66:237–41.

    Article  CAS  PubMed  Google Scholar 

  72. Cruz-Soto ME1, Scheiber MD, Gregerson KA, Boivin GP, Horseman ND. Pituitary tumorigenesis in prolactin gene-disrupted mice. Endocrinology. 2002;143:4429–4436.

  73. Schuff KG, Hentges ST, Kelly MA, Binart N, Kelly PA, Iuvone PM, et al. Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms. J Clin Invest. 2002;110:973–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Asa SL, Kelly MA, Grandy DK, Low MJ. Pituitary lactotroph adenomas develop after prolonged lactotroph hyperplasia in dopamine D2 receptor-deficient mice. Endocrinology. 1999;140:5348–55.

    Article  CAS  PubMed  Google Scholar 

  75. Biondi M, Picardi A. Psychological stress and neuroendocrine function in humans; the last two decades of research. Psychoter and Psychosom. 1999;68:114–50.

    Article  CAS  Google Scholar 

  76. Sobrinho LG, Simoes M, Barbosa L, Raposo JF, Pratas S, Fernandes PL, et al. Cortisol, prolactin, growth hormone and neurovegetative responses to emotions elicited during an hypnoidal state. Psychoneuroendocrinology. 2003;28:1–17.

    Article  CAS  PubMed  Google Scholar 

  77. Lennartsson AK, Jonsdottir IH. Prolactin in response to acute psychosocial stress in healthy men and women. Psychoneuroendocrinology. 2011;36:1530–9.

    Article  CAS  PubMed  Google Scholar 

  78. Corenblum B, Whitaker M. Inhibition of stress-induced hyperprolactinemia. Brit Med J. 1977;2:1328.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Wieschhoff HA. Artificial stimulation of lactation in primitive cultures. Bull Hist Med. 1940;8:1403–15.

    Google Scholar 

  80. Scarpa A. Etnomedicina. Milan: Franco Lucisano Editore; 1980.

    Google Scholar 

  81. Reichlin S. Prolactin and growth hormone secretion in stress. In: Chrousos GP, Loriaux DL, Gold PW, editors. Mechanisms of physical and emotional stress. New York: Plenum Press; 1988. p. 353–76.

    Chapter  Google Scholar 

  82. Voith VL. Functional significance of pseudocyesis. Mod Vet Pract. 1980;61:75–7.

    CAS  PubMed  Google Scholar 

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  1. Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Rua Prof. Lima Basto, 1063–093, Lisbon, Portugal

    Luis G. Sobrinho

  2. University of Cincinnati College of Medicine, Cincinnati, OH, 45267-0576, USA

    Nelson D. Horseman

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Sobrinho, L.G., Horseman, N.D. Prolactin and human weight disturbances: A puzzling and neglected association. Rev Endocr Metab Disord 20, 197–206 (2019). https://doi.org/10.1007/s11154-019-09503-1

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