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Original Studies |
-Chain Messenger Ribonucleic Acids That Are Regulated by GnRH in Vitro1
Department of Obstetrics and Gynecology, National Taiwan University Hospital (H.-F.C.), Taipei, Taiwan; the Laboratory of Veterinary Biochemistry, Chungbuk National University (E.-B.J.), Cheong-ju, Korea; and the Department of Obstetrics and Gynecology, University of British Columbia (M.S., P.C.K.L.), Vancouver, British Columbia, Canada V6H 3V5
Address all correspondence and requests for reprints to: Dr. P. C. K. Leung, Department of Obstetrics and Gynecology, 4490 Oak Street, Vancouver, British Columbia, Canada V6H 3V5. E-mail: peleung{at}unixg.ubc.ca
The hypothalamic decapeptide, GnRH, plays a critical role in human
reproduction. In addition to the well known effects of GnRH on
pituitary cells, there is evidence supporting the presence of
GnRH-binding sites in tissues other than pituitary cells, including
lymphocytes. In addition, a GnRH-like substance has been found to be
secreted from lymphoid cells. However, the precise nature of GnRH
secretion and binding in immune cells has not been fully established.
In this study, we used the RT-PCR method to examine the expression and
regulation of GnRH, GnRH receptor (GnRHR), and interleukin-2 receptor
-chain messenger ribonucleic acids (mRNAs) in human peripheral blood
mononuclear cells. It was found that human mononuclear cells expressed
GnRH and GnRHR mRNAs. Nucleotide sequences of these mRNAs are identical
to their hypothalamic and pituitary counterparts, respectively. In
addition, GnRH and GnRHR mRNA expressions in peripheral blood
mononuclear cells are regulated by GnRH and its synthetic analogs
in vitro. Treatment with various concentrations of GnRH
(10-5-10-11 mol/L) increased GnRHR mRNA
expression in a dose-dependent manner (maximal level is 158% of the
untreated control value at 10-8 mol/L GnRH;
P < 0.05), but reduced GnRH mRNA levels to 69% of
the untreated control value at 10-9 mol/L GnRH
(P < 0.05). Cotreatment of GnRH with a GnRH
antagonist blocked these regulatory effects, indicating the
receptor-mediated nature of the GnRH action. Both GnRH and GnRH
agonist stimulated interleukin-2 receptor -chain mRNA in a
dose-dependent manner, indicating that GnRH may be involved in
lymphocyte activation. In summary, these observations suggest that
mRNAs encoding the pituitary form of GnRHR and the hypothalamic form of
GnRH are also expressed in human peripheral blood mononuclear cells.
The endogenous production of GnRH by lymphocytes may act as an
autocrine or paracrine factor to regulate immune functions. Because of
the presence of GnRHR on lymphocytes, exogenous GnRH analog therapy may
have an impact on the immune system through these receptors.
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