The presented results speak for the direct effects of

The presented results speak for the direct effects of ghrelin on rat spermatozoa, which are accomplished by the activation of the GHSR-1a receptor. Thus, the results seem to be of physiological significance in vivo since ghrelin, the natural ligand of GHSR-1a, was found to be present in the seminal plasma, at least in humans [32]. However, the indirect effects of ghrelin on sperm function should also be mentioned since a report was published on the improvement of the viability of rat spermatozoa in vitro as a result of ghrelin administration to rats in vivo[33]. The authors treated 45-day-old rats with 1nmol of ghrelin daily for 10 days and found both increased spermatozoa progressive movement values and increased membrane integrity which could be observed up to 40 days after the last injection. However, because ghrelin possesses multiple functions, these results may be a consequence of its action at different levels of the neuro-endocrine axis which controls reproductive functions in rats. In discussing the dose-dependence of ghrelin on rat spermatozoa in vitro, the problem of cell response to the increasing concentration of the peptide present in the incubation medium should be taken into account. In this paper we report a reduction in the percentage of the spermatozoa progressive movement when the concentration of ghrelin in the medium was increased to 10−4mol/L. This effect may be caused by the down-regulation of the ghrelin receptor in spermatozoa. The in vivo effects of experimental hyperghrelinemia have been demonstrated in prepubertal male rats, showing a decrease in serum LH and testosterone levels and delayed timing of puberty [18]. Hyperghrelinemia associated with impairment of the neuroendocrine axis and gonadal function has also been observed in humans with Prader–Willi syndrome [17], [34]. In conclusion, in this study we reported the glucagon receptor of the ghrelin receptor in rat spermatozoa and in vitro response of the spermatozoa to ghrelin. The receptor function was dependent on ligand concentration, and included protection of sperm viability and increase in sperm motility. These phenomena occurred optimally at 10−6mol/L of ghrelin concentrations. Higher concentration of ghrelin (10−4mol/L) had an opposite effect on sperm motility. Thus, our report includes spermatozoa as a site of ghrelin signal reception in the male reproductive system, at least in rats, and raises the question of whether this system also exists in the male gametes of other species, including humans.
Acknowledgment This research was supported by grant number 3951/P01/2006/31 from the Ministry of Science and Higher Education, Poland.
Introduction Ghrelin is a 28 amino acid acylated peptide that was first isolated from the rat's gastric mucosa. It is the endogenous ligand of the somatosecretagogue's receptor type 1a (GHSR-1a), promoting growth hormone release from the pituitary. Ghrelin derives from a 117 preprohormone named preproghrelin [9]. Preproghrelin is further processed and can originate other peptides such as obestatin and des-acyl ghrelin [19]. Ghrelin is an orexigenic peptide that exerts effects in numerous organ systems such as the endocrine, cardiovascular, pulmonary, gastrointestinal, immune, ocular and others [13]. Des-acyl ghrelin is a peptide similar to ghrelin but lacks the acyl group at SER 3, and is unable to bind the GHSR-1a [3], [5]. When compared to ghrelin, des-acyl ghrelin can exert contrary, analogous or independent effects [19]. The GHSR gene can originate two isoforms of the receptor: a full length isoform composed of 7 transmembrane domains named GHSR-1a; and, a truncated isoform with only 5 transmembrane domains named GHSR-1b [6], [14]. Although the two isoforms have been described, only GHSR-1a is able to bind ghrelin or its analogs [6]. Recently, both ghrelin and des-acyl ghrelin have been implicated in ocular physiology. Ghrelin is able to relax both the iris sphincter and dilator muscles. In the sphincter, the effect is mediated by prostaglandins release. This effect is independent from nitric oxide and the GHSR-1a receptor. However, the effects on the dilator muscle are mediated by GHSR-1a stimulation [18]. Furthermore, ghrelin's mRNA has been detected in the non-pigmented epithelium of the ciliary body and in the posterior epithelium of the iris [18]. Ghrelin has been detected in the aqueous humor and its levels are decreased in patients suffering from different glaucoma types [8], [16].