Ghrelin Expression in Human Testis and Serum Testosterone Level

Abstract

Ghrelin, which is the endogenous ligand for the growth hormone (GH) secretagogue receptor (GHS-R), has been primarily linked to the central neuroendocrine regulation of GH secretion and food intake, although additional peripheral actions of ghrelin have also been reported. Recent research has suggested that ghrelin also affects testosterone (T) secretion in vitro. To investigate the role of ghrelin in human testicular function, we examined the expression of ghrelin in testicular tissues by immunohistochemistry. Testicular tissue samples were collected from the testes of 5 fertile volunteers, 8 patients with obstructive azoospermia, and 36 oligospermic patients with varicocele testis. In the testicular tissues, ghrelin was stained using the antighrelin polyclonal antibody, and the Johnsen sco re w as ca lcu la te d. Th e con cent ra ti on s o f ser um follicle-stimulating hormone (FSH), lutenizing hormone (LH), and T were determined by chemiluminescence assays. Immunostaining of ghrelin was detected in the interstitium and in Leydig cells. Ghrelin expression by Leydig cells was inversely correlated with the serum T concentration (r 5 2.50; P , .001), but was not directly related to spermatogenesis. We conclude that steroidogenic dysfunction is associated with increased ghrelin expression in human testes.Key words: Leydig. J Androl 2007;28:320-324 G hrelin has recently been identified as the endogenous ligand for the growth hormone (GH) secretagogue receptor (GHS-R) (Kojima et al, 1999; Kojima et al, 2002). Ghrelin is a 28-amino acid peptide with an essential n-octanoyl modification at Ser3. This peptide is primarily expressed in the stomach and hypothalamus (Kojima et al, 1999; Kojima et al, 2002). As expected for an endogenous ligand of GHS-R, ghrelin elicits GH secretion in vivo and from anterior pituitary cells in culture (Kojima et al, 1999;Takaya et al, 2000;Wren et al, 2000). In addition to its role in the control of GH release, ghrelin, probably derived from a stomach source and acting on hypothalamic centers, has recently been shown to induce a number of biological responses at the central neuroendocrine level, including stimulation of food intake and adiposity (Kamegai et al, 2000;Takaya et al, 2000;Wren et al, 2000). The biological effects of ghrelin identified to date are executed at the central levels of the hypothalamus and pituitary. In addition to these central biological effects, there is growing evidence for peripheral actions of ghrelin. In this regard, the novel expression of ghrelin in noncentral tissues, such as the ovary and kidney, is of interest (Tschop et al, 2000;Gaytan et al, 2003).Moreover, it has been shown that ghrelin and its functional receptor are expressed in rat and human testes Tena-Sempereet al, 2002; Gaytan et al, 2004). Testicular function is critically dependent upon the interaction of a plethora of endocrine, paracrine, and autocrine regulatory signals (Skinner MK, 1991;Saez JM, 1994). It has become evident that different factors with key roles in growth axis...

Cloning of a novel insulin-regulated ghrelin transcript in prostate cancer

“…In2c-ghrelin is expressed in all normal testis samples examined, while it is expressed in a small number of testicular tumours. This correlates well with previous studies, which have shown that the ghrelin peptide is present in normal human testis (Gaytan et al 2004, Ishikawa et al 2007) and in a subset of testicular tumours (Gaytan et al 2004). Employing a small number of normal samples, we also demonstrate that in2c-ghrelin is expressed in breast and ovarian tumours but not in normal breast or ovary.…”

The effects of streptozotocin-induced diabetes on ghrelin expression in rat testis: biochemical and immunohistochemical study

“…Duran et al [41] demonstrated decreased serum Ghrelin levels in idiopathic hypogonadotropic hypogonadism (IHH) patients who also had lower serum LH and testoste- [42] demonstrated that when the serum testosterone levels were increased, serum ghrelin level was increased significantly. Ishikawa et al [43] demonstrated that expression of ghrelin by Leydig cells is inversely correlated with the serum T concentration. Also they have proposed that ghrelin has not directly related on spermatogenesis.…”

Immunohistochemical and hybridocytochemical study on ghrelin signalling in the rat seminiferous epithelium.

“…In human spermatogenic cells, especially in pachytenes, they localized GHSR-1a protein. Controversially, other researchers demonstrated ghrelin immunohistochemically in pachytene spermatocytes of human [36] and ovine testis [43].…”

“…Spermatocytes in human, rat and ovine testis expressed ghrelin and GHSR-1a and authors suggested that ghrelin can influence spermatogenesis acting via Leydig cells and may operate as a local regulator in the fine-tuning of spermatogenic function [36], however, without exception of the possibility that ghrelin may regulate gene expression of local modulators in the rat seminiferous tubules [32,34]. Appreciating the above novel data reflecting role of the peptide and its receptor in control of male gonad function via Leydig cells we intend to consider the gathered results of own studies in light of the local regulatory mechanism for the course of spermatogenesis within the cycle of seminiferous epithelium.…”

“…Thus, target cells are expected to respond to both exogenous and endogenous ghrelin, the last being involved in local paracrine/autocrine regulatory mechanism modulating cell function including target cells in testis. In human and mammalian testis the gene expression for both ghrelin and GHSR-1a was evidenced [28] and the cells with ghrelin and GHSR-1a expression in testis were documented although physiological role of these proteins in seminiferous epithelium seems to need further elucidation [21,[29][30][31][32][33][34][35][36].…”