Expression of gonadotropin-releasing hormone type-I (GnRH-I) and type-II (GnRH-II) in human peripheral blood mononuclear cells (PMBCs) and regulation of B-lymphoblastoid cell proliferation by GnRH-I and GnRH-II.
GnRH-I and its receptor (GnRHR-I) have previously been demonstrated and shown to be biologically active in the immune system, notably within T cells. Recently however a second form of GnRH (GnRH-II) has been described in the human. The function of both these neuropeptides in B lymphocytes has not previously been explored. The present study investigates GnRH-I and GnRH-II expression in human peripheral mononuclear blood cells (PMBCs) and B lymphoblastoid cells (B-LCLs), as well as their action in regulating B-LCL proliferation in the presence and absence of interleukin-2 (IL-2), both in GnRHR-I mutated lymphocytes and in a normal control. RT-PCR and immunocytochemistry identified locally produced GnRH-I and GnRH-II in all cell groups. Treatment of normal B-LCLs with GnRH-I (10 (-9) M and 10 (-5) M) or with interleukin-2 (IL-2) (50 IU/ml) resulted in a significant increase in cell proliferation compared with the untreated control. IL-2 and GnRH-I (10 (-7) M, 10 (-6) M, 10 (-5) M) induced greater proliferation in normal B-LCLs than IL-2 treatment alone. No significant proliferation occurred in GnRHR-I defective B-LCLs, in response to either GnRH-I (10 (-9) and 10 (-5) M) or IL-2 treatment, nor to IL-2 and GnRH-I (10 (-10) to 10 (-5) M) co-treatment when compared to controls. Co-incubation of IL-2 and IL-2 + GnRH 10 (-5) M with a GnRH antagonist (Cetrorelix; 10 (-6) M) significantly attenuated the proliferation in normal B-LCLs. GnRH-II did not affect proliferation of normal B-LCLs alone, and did not alter the proliferative response to IL-2. Further investigation is required to clarify the physiological relevance of local GnRH-I/GnRH-II in immune system responsiveness.
Tanriverdi
F
F
Department of Endocrinology, Erciyes University Medical School, Talasyolu, Kayseri, Turkey. fatihtan@erciyes.edu.tr
Gonzalez-Martinez
D
D
Silveira
L F G
LF
Hu
Y
Y
Maccoll
G S
GS
Travers
P
P
Bouloux
P M G
PM
D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000235:genetics* / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007376:Interleukin-2; D007987:Gonadotropin-Releasing Hormone; C047717:LHRH, His(5)-Trp(7)-Tyr(8)-