The hypothalamic-pituitary-gonadal axis is fundamental to the control of reproductive functions, whose main actor is the hypothalamic gonadotropin releasing hormone. Released into the hypophyseal portal vasculature from axon terminals at the median eminence. Intermittent GnRH secretion from the hypothalamus acts upon the GnRH receptor in the anterior pituitary to regulate the production and secretion of gonadotropins EX 527 HDAC inhibitor including LH and FSH that in turn regulate development and activity of the testes. The pituitary requires pulsatile stimulation by GnRH to synthesize and release the gonadotropins LH and FSH, in turn, the feedback from gonadotropins finely modulate the GnRH release. Moreover, the GnRH secretion depends on the activation of the GPR54, located on the surface of the GnRH neurons and stimulated by the peptide kisspeptin which is a product of the Kiss-1 gene. In the present study, alterations in the GnRH1 gene expression were observed after i.p. injection of MC-LR, suggesting that MC-LR affected the reproductive system by means of actions at the level of the hypothalamus through modulation of GnRH synthesis and / or release. A lower GnRH secretion to the hypophyseal portal blood would result in the reduction of LHb synthesis, which caused the decreasing testosterone production in the testis. GnRH could affect the GnRHR gene expression directly at the pituitary level. However, in the present study, the GnRHr mRNA levels kept unchanged. The mechanism awaits to be elucidated in our future study. In addition, no variations of GPR54 and Kiss-1 mRNA expression were observed in the study, indicating that MR-LR may not affect the GPR54/Kiss-1 regulation system directly. The gonadotrope cell of the anterior pituitary plays a particularly critical role within the HPG axis system as the intermediary between the hypothalamic GnRH signal and the steroid hormone productivity of the gonads. FSH and LH stimulate sex steroid production and secretion in the gonads. These molecules then feed back to the brain and pituitary to regulate the gonadotropins. In general, androgens have negative feedback effects primarily on the release of GnRH from the hypothalamus, which then suppresses both FSH and LH secretion. When serum testosterone level is reduced, the GnRH synthesis and secretion increases followed by a subsequent rise in the synthesis and secretion of LH from the pituitary gland. In the present study, MC-LR administration to mice resulted in a reduction in the serum testosterone concentration in a dose- and time- dependent manner. Intriguingly, the serum LH synthesis and secretion were reduced as well. Such phenomenon could be explained by the assumption that the possible increase in GnRH expression stimulated by the decreased testosterone level had been offset by the inhibited GnRH synthesis caused by exposure to MC-LR, which further demonstrate that the primary target of MC-LR is GnRH and MC-LR would disrupt the GnRH expression directly or indirectly.