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

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.

The Significance of Vasoactive Intestinal Peptide in Immunomodulation

“…In 1980, it was shown that macrophages and lymphocytes were able to produce adrenocorticotropin and endorphins (Blalock and Smith, 1980;Smith and Blalock, 1981). To date, immune cells produce around 30 neuroendocrine mediators, including growth hormone (Weigent et al, 1988), prolactin (Montgomery et al, 1987), proenkephalin A (Rosen et al, 1989), somatostatin (Fuller and Verity, 1989;, oxytocin-vasopressin (Geenen et al, 1987), atrial natriuretic peptide (Vollmar et al, 1992), substance P (Ho et al, 1997;Lai et al, 1998;Lambrecht et al, 1999), gonadotropin-releasing hormone (Chen et al, 1999), glucocorticoids (Lechner et al, 2000), procalcitonin (Oberhoffer et al, 1999), corticotropin-releasing factor (CRF) (Brouxhon et al, 1998), vasoactive intestinal peptide (VIP; see Section II. ), pituitary adenylate cyclase-activating polypeptide (PACAP) , neuropeptide Y (Schwarz et al, 1994), calcitonin gene-related peptide (CGRP) (Singaram et al, 1991), ␣-melanocyte-stimulating hormone (␣MSH) (Lolait et al, 1986;Rajora et al, 1996), and opioid peptides (Przewlocki et al, 1992).…”

Molecular cloning and differential expression of three GnRH mRNAs in discrete brain areas and lymphocytes in red drum

“…The finding of GnRH-I mRNA and peptide expression in red drum lymphocytes appears to be consistent with GnRH-I mRNA expression in tissues of the mammalian immune system, such as lymphocytes, thymocytes, thymus, and spleen (Azad et al 1991a,b 1993, Maier et al 1992, Chen et al 1999. In addition, both GnRH-I and GnRH-II are expressed in human T cells (Chen et al 2002).…”

“…GnRH-I expression has been reported also in a variety of mammalian non-neural tissues such as bone marrow, gastric smooth muscle cells, gonads, heart, incisors, kidney, liver, pancreas, placenta, prostate, and skeletal muscle (Dolan et al 2003, Chen et al 2004, Tiong et al 2004. In addition, GnRH-I expression and GnRH binding sites have been demonstrated in different tissues of the immune system of mammals (Chen et al 1999). Similarly in teleosts, GnRH-I expression has been shown in gill, gonad, heart, kidney, liver, muscle, pituitary, and spleen (Ferriere et al 2001, Mohamed et al 2005.…”

Identification of the Expression Level to LH-r Gene In dominant and Cystic Ovarian Follicles Cells of the Cows

“…The q(rt-PCR) was performed by using AccuPower® Greenstar™ qPCR PreMix reagent kit (Bioneer, Korea) and Exicycler™ 96 Real-Time Quantitative Thermal Block (Bioneer, Korea), according to method described by Chen HF [22]. The SYBER Green I based q(rt-PCR) premix reagent kit is designed for PCR amplification of cDNA for target gene by using LH-r primer and housekeeping gene (GAPDH).…”