Inhibitory action of melatonin and structurally related compounds on testosterone production by mouse leydig cells in vitro

Abstract

The possible effect of melatonin, 5-methoxytryptamine, 5-methoxytryptophol, 6-chloromelatonin and 2-iodomelatonin on testosterone production by Leydig cells in vitro was investigated. The ability of individual indoles to inhibit testosterone production was found to depend on the concentration used. The relative inhibitory potency of the compounds tested was: 6-chloromelatonin greater than 2-iodomelatonin greater than melatonin greater than 5-methoxytryptamine greater than 5-methoxytryptophol. The results revealed that natural indoles which are synthesized in the pineal gland and their halogenized derivatives are capable of influencing directly testosterone production by Leydig cells. Also, these results demonstrated that melatonin exerts its remarkable antigonadotrophic effects, at least in part, through the direct decrease of testosterone production. Moreover, 6-chloromelatonin and 2-iodomelatonin, which are reported to inhibit melatonin binding to target tissues, possess properties of biological melatonin analogues under the conditions of the model system used.

Melatonin Inhibits Apoptosis and Oxidative Stress of Mouse Leydig Cells via a SIRT1-Dependent Mechanism

“…In addition, melatonin can directly act on the testis and ameliorate testicular damages caused by oxidative stress, apoptosis, and inflammation [17,18,19,20]. Significantly, past research has depicted that melatonin reduces testosterone secretion in mouse Leydig cells [21,22]. However, the effects of melatonin on apoptosis and oxidative stress in mouse Leydig cells and its mechanisms have not been examined.…”

2-[¹²⁵I]Iodomelatonin Binding Sites in the Testis and Ovary: Putative Melatonin Receptors in the Gonads

“…In the adult rat, melatonin was demonstrated to significantly potentiate the regression of testes following hypophysectomy [20], The inhibitory nature of melatonin on steroidogenesis in testicular tissue is thought to result from interference in the bio synthetic pathway of testosterone [21,22], possibly in the Leydig cell fraction [23], Fur ther affirmation that the Leydig cells may be the target site for melatonin in the testes is suggested by the inhibitory effect of melaton in on testosterone production by Leydig cells in vitro [24] and alterations in cellular andro gen secretion and morphology following mela tonin treatment in mice [25], It also appears that the impact of melatonin on the Leydig 72 Ayre/Pang Melatonin Receptors in Gonads cell fraction may be dependent upon seasonal and circadian variables [26,27]. The evidence that melatonin acts directly on isolated rat Leydig cells to inhibit LH-induced testoster one production and does not act on LH recep tors located in the Leydig cells supports the argument for specific melatonin receptors in the testes [28], In the human ovary, melatonin has been shown to modulate steroidogenesis directly through increased synthesis of steroid hor mones by corpus luteum and stromal tissue in vitro [29].…”

“…Although the homo geneity of 2-[125l]iodomelatonin labelling in the autoradiography study suggests that bind ing sites were situated on the majority of tes ticular tissues, it could be possible that due to the limits of film resolution, it is difficult to detect binding to a population of functionally related but anatomically dispersed cells. It is likely that 2-[125I]iodomelatonin may be bind ing to Leydig cells which are widely distribut ed throughout the testes and have been pro posed as the target site for melatonin action in the testes [23][24][25]27], In the chicken, duck and quail ovary, 2-[l25I]iodomelatonin bind ing was clearly concentrated around the folli cles in which cells of granulosa membrane are known to proliferate. As melatonin has been documented to have a direct effect on granu losa cell steroid hormone production [30,31] it is possible that 2-[125I]iodomelatonin may be labelling putative melatonin receptors lo cated in the granulosa cell fraction.…”

Daily variation in the concentration of 5‐methoxytryptophol and melatonin in the duck pineal gland and plasma

“…Although the presence of 5‐methoxytryptophol has been demonstrated in pineal glands of various animals and humans (Skene et al., 1986, 1987, 1989, 1990, 1991; Lakhdar‐Ghazal et al., 1992; Vivien‐Roels et al., 1992, 1999; Hofman et al., 1995; Zawilska et al., 1998, 2000), its physiological role in an organism still remains to be clarified. It has been demonstrated that 5‐methoxytryptophol can stimulate or inhibit gonadal activity, depending on the species, the sex of the animal, and the photoperiod/season (Pévet, 1985; Joy and Agha, 1991; Ooi and Ng, 1989; Persengiev and Kehajova, 1991; Raynaud et al., 1991; Ng and Chan, 1993). The observation of significant age‐ and sex‐dependent changes in plasma 5‐methoxytryptophol levels in children has led to a hypothesis that, in addition to melatonin, this pineal hormone may be involved in the developmental processes in humans (Molina‐Carballo et al., 1996).…”