Human Peripheral Blood Mononuclear Cells Express Gonadotropin-Releasing Hormone (GnRH), GnRH Receptor, and Interleukin-2 Receptor γ-Chain Messenger Ribonucleic Acids That Are Regulated by GnRH in Vitro 1

Abstract

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 gamma-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 gamma-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.