Prolactin (PRL) secretion by the pituitary is under the control of dopamine. Hyperprolactinemia has been found in patients with systemic lupus erythematosus (SLE) and seems to be associated with clinical activity. T-lymphocytesexpress PRL and those from SLE patients appear to secrete more PRL than controls. In this study, immuno-(RIA) and bio-(BIO) assayable PRL in both serum and culture media of peripheralblood mononuclearcells (PBMNC) from SLE and control subjectswere evaluated in the basal state and in response to 10 mg oral administration of metoclopramide, a dopamine receptor antagonist. Prolactin size heterogeneity in serum and culture media and PRL gene transcription in PBMNC were also studied. Basal serum RIA-PRL, BIO-PRL and the BIO/RIA ratio were similar in both groups. The serum BIO-PRL response after metoclopramide was higher than RIA-PRL in SLE, and this increment was also greater than in control subjects. PBMNC from SLE subjects secreted and produced more BIO-PRL. After metoclopramide, secretion and production of PRL increased only in PBMNC from control women and not in those from SLE patients. Our results demonstrated an increased central dopaminergic tone in SLE and suggest that lymphocyte-derived PRL might contribute to alter the functionalactivity of the hypothalamicdopaminergicsystem in SLE attempting to maintain serum PRL within a physiological range.
Berczi I , Nagy E.Prolactin and other lactogenic hormones. In: Berczi I (ed) Pituitary and Immunity. CRC Press Inc: Boca Raton, FL , 1986, 161-183.
2.
Matera L , Mori M , Geuna M , Buttiglieri S , Palestro G.Prolactin in autoimmunity and antitumor defense . J Neuroimmunol2000; 109: 47-55 .
3.
Nagy E , Berczi I , Friesen HG.Regulation of immunity in rats by lactogenic and growth hormones . Acta Endocrinol (Copenh)1983; 102: 351-357 .
4.
Russell DH , Kibler R , Matrisian L , Larson DF , Poulos B , Magun RE.Prolactin receptors on human T and B lymphocytes: Antagonism of prolactin binding by cyclosporin . J Immunol1985; 134: 3027-3031 .
5.
Matera L , Muccioli G , Cesano A , Bellussi G , Genazzani E.Prolactin receptors on large granular lymphocytes: Dual regulation by cyclosporin A . Brain Behav Immunol1988; 2: 1-10 .
6.
Sabharwal P , Glaser R , Lafuse W , Varma S , Liu Q , Arkins Set al.Prolactin synthesized and secreted by human peripheral blood mononuclear cells: An autocrine growth factor for lymphoproliferation . Proc Natl Acad Sci USA1992; 89: 7713-7716 .
7.
Larrea F , Martínez-Castillo A , Cabrera V , Alcocer-Varela J , Queipo G , Cariño Cet al.Alarcón-Segovia D.A bioactive 60-kilodalton prolactin species is preferentially secreted in cultures of mitogen-stimulated and nonstimulated peripheral blood mononuclear cells from subjects with systemic lupus erythematosus . J Clin Endocrinol Metab1997; 82: 3664-3669 .
8.
Nagy E , Berczi I.Hypophysectomized rats depend on residual prolactin for survival . Endocrinology1991; 128: 2776-2784 .
9.
Matera L.Endocrine, paracrine and autocrine actions of prolactin in immune cells . Life Sci1996; 59: 599-614 .
10.
Jara LJ , Gómez-Sánchez C , Silveira LH , Martínez-Oxuna P , Vasey FB , Espinoza LR.Hyperprolactinemia in systemic lupus erythematosus: association with disease activity . Am J Med Sci1992; 303: 222-226 .
11.
Neidhart M.Elevated serum prolactin or elevated prolactin/cortisol ratio are associated with autoimmune processes in systemic lupus erythematosus and other connective tissue diseases . J Rheumatol1996; 23: 476-481 .
12.
Jacobi AM , Rohde W , Ventz M , Riemekasten G , Burmester G-R , Hiepe F.Enhanced serum prolactin (PRL) in patients with systemic lupus erythematosus: PRL levels are related to the disease activity . Lupus2001; 10: 554-561 .
13.
Berwaer M , Martial JA , Davis JRE.Characterisation of an upstream promoter directing extrapituitary expression of the human prolactin gene . Mol Endocrinol1994; 8: 635-642 .
14.
Gutiérrez MA , Molina JF , Jara LJ , Cuéllar ML , García C , Gutiérrez-Ureña Set al.Prolactin and systemic lupus erythematosus: prolactin secretion by SLE lymphocytes and proliferative (autocrine) activity . Lupus1995; 4: 348-352 .
15.
Tan EM , Cohen AS , Fries JF , Masi AT , McShane DJ , Rothfield NFet al.The 1982 revised criteria for the clasification of systemic lupus erythematosus . Arthritis Rheum1982; 25: 1271-1277 .
16.
Guzmán J , Cradiel MH , Arce-Salinas A , Sánchez-Guerrero J , Alarcón-Segovia D.Measurement of disease activity in systemic lupus erythematosus. Prospective validation of 3 clinical indices . J Rheumatol1992; 19: 1551-1558 .
17.
Larrea F , Sandoval JL , Salinas E , Franco-Rodríguez VA , Méndez I , Ulloa-Aguirre A.Evidence for an altered luteinizing hormone sensitivity to naloxone in pathological hyperprolactinaemia . Clin Endocrinol (Oxf)1995; 43: 591-600 .
18.
Tanaka T , Shiu RPC , Gout PW , Beer CT , Noble RL , Friesen HG.A new sensitive and specific bioassay for lactogenic hormone measurement of prolactin and growth hormone in human serum . J Clin Endocrinol Metab1980; 51: 1058-1063 .
19.
Sinha YN , Gilligan TA , Lee DW.Detection of high molecular weight variant of prolactin in human plasma by a combination of electrophoretic and immunological technics . J Clin Endocrinol Metab1984; 58: 752-754 .
20.
Laemmli UK.Cleavage of structural proteins during the assembly of the head of bacteriophage T4 . Nature1970; 227: 680-685 .
21.
Chomczynski P , Sacchi N.Single step method of RNA isolation by acid guanidiniumthiocyanate-phenol-chloroform extraction . Anal Biochem1987; 162: 156-159 .
22.
Maniatis T , Jeffrey A , van der Sande H.Chain length determination of small double and single-stranded DNA molecules by polyacrylamide gel electrophoresis . Biochemistry1975; 14: 3787-4394 .
23.
Cooke NE , Coit D , Shine J , Baxter JD , Martial JA.Human prolactin, cDNA structural analysis and evolutionary comparisons . J Biol Chem1981; 256: 4007-4016 .
24.
Quigley ME , Judd SJ , Gilliland GB , Yen SSC.Effects of a dopamine antagonist on the release of gonadotropinand prolactin in normal women and in women with hyperprolactinemic anovulation . J Clin Endocrinol Metab1979; 48: 718-720 .
25.
Parra A , Barron J , Sinibaldi J , Coria I , Espinosa de los Monteros A.Differences in the metoclopramide-induced prolactin release related to age at first full-term pregnancy or nulliparity . Hum Reprod1997; 12: 214-219 .
26.
Parra A , Ramirez-Peredo J , Larrea F , Cabrera V , Coutiño B , Torres Iet al.Decreased dopaminergic tone and increased basal bioactive prolactin in men with human immunodeficiency virus infection . Clin Endocrinol2001; 54: 731-738 .
27.
Zoli A , Ferlisi EM , Pompa A , Barini A , Altomonte L , Mirone L , Magaro M.Basal and after-stimuli test for prolactinemia in systemic lupus erythematosus . Ann NY Acad Sci1999; 876: 155-158 .
28.
Takemoto M , Morishita H , Higuchi K , Yoshida J , Aono T.Effects of body weight on responses of serum prolactin to metoclopramide and thyrotropin-releasing hormone in secondary amenorrhoeic women . Hum Reprod1994; 9: 800-805 .
29.
Ferreira C , Paes M , Gouveia A , Ferreira E , Pádua F , Fiuza T.Plasma homovanillic acid and prolactin in systemic lupus erythematosus . Lupus1998; 7: 392-397 .
30.
Ben-Jonathan N.Dopamine: a prolactin-inhibitinghormone . Endocr Rev1985; 6: 564-589 .
31.
Candito M , Durant J , Gurle V , Chambon P , Dallamonica P.Cerebrospinalfluid 5-hydroxyindoleacetic acid and homovanillic acid in AIDS dementia complex . AIDS1995; 9: 1100-1101 .
32.
Blanco-Favela F , Chávez-Rueda K , Leaños-Miranda A.Analysis of anti-prolactin antibodies in systemic lupus erythematosus . Lupus2001; 10: 757-761 .
33.
Bucala R , Lahita RG , Fishman J , Cerami A.Increased levels of 16 alpha-hydroxyestrone-modified proteins in pregnancy and in systemic lupus erythematosus . J Clin Endocrinol Metab1985; 60: 841-847 .
34.
Jara LJ , Prasad C , Espinoza LR.Elevated serum levels of cyclo (His-Pro), an endogenous inhibitor of pituitary prolactin secretion, in systemic lupus erythematosus patients . Lupus1997; 6: 258-260 .
35.
Spangalo BL , Judd AM , Isakson PC , McLeod RM.Interleukin-6 stimulates anterior pìtuitary hormone release in vitro . Endocrinology1989; 125: 575-577 .
36.
Gutiérrez MA , Anaya JM , Scopelitis E , Citera G , Silveira L , Espinoza LR.Hyperprolactinaemia in primary Sjogren’s syndrome . Ann Rheum Dis1994; 53: 425-425 .
37.
El-Graf A , Salah S , Shaarawg M , Zaqui S , Anwer S.Prolactin hormone in juvenile systemic lupus erythematosus: a possible relationship to disease activity and SNC manifestations . J Rheumatol1996; 23: 374-377 .
38.
Baranzini SE , Elfstrom C , Chang SY , Butunoi C , Murray R , Higuchi R , Oksenberg JR.Transcriptional analysis of multiple sclerosis brain lessions reveals a complex pattern of cytokine expression . J Immunol2000; 165: 6576-6582 .
39.
Nagafuchi H , Suzuki N , Kaneko A , Asai T , Sakane T.Prolactin locally produced by synovium infiltrating T lymphocytes induces excessive synovial cell functions in patients with rheumatoid arthritis . J Rheumatol 199; 26: 1890-1900 .
40.
Reem GH , Ray DW , Davis JRE.The human prolactin gene upstream promoter is regulated in lymphoid cells by activators of T-cells and cAMP . J Mol Endocrinol1999; 22: 285-293 .
41.
Stevens A , Ray DW , Worthington J , Davis JRE.Polymorphisms of human prolactin gene: implications for production of lymphocyte prolactin in systemic lupus erythematosus . Lupus2001; 10: 676-683 .
42.
Zheng W , Flavell RA.The transcription factor GATA-3 is necessary and sufficient for the Th2 cytokine gene expression in CD4 T cells . Cell1997; 89: 587-596 .
43.
Gellersen B , Kempf R , Telgmann R , DiMattia GE.Nonpituitary human prolactin gene transcription is independent of Pit-1 and differentially controlled in lymphocytes and in endometrial stroma . Mol Endocrinol1994; 8: 356-373 .
44.
Matera L , Bellone G , Lebren JJ , Kelly PA , Hooghe-Peters EL , DiCelle PFet al.Role of prolactin in the in vitro development of interleukine-2- driven anti tumoral lymphokine-activated killer cells . Immunology1996; 89: 619-626 .
45.
Santambrogio L , Lipartiti M , Bruni A , Dal Toso R.Dopamine receptors on human T- and B-lymphocytes . J Neuroimmunol1993; 45: 113-120 .
46.
Walker SE.Treatment of systemic lupus erythematosus with bromocriptine . Lupus2001; 10: 197-202 .
