Effect of manganese on luteinizing hormone-releasing hormone secretion in adult male rats

Recently studies have demonstrated that low doses of (Mn+2) in the form of manganese chloride can stimulate specific puberty-related hormones and advance signs of pubertal development in immature female and male rats. In the present study, we used an in vitro system to evaluate the ability of 0, 50, 250, and 500 mu M doses of Mn+2 to stimulate luteinizing hormone-releasing hormone (LHRH) secretion and to assess the hypothalamic mechanism of this action in adult male Sprague-Dawley rats. We demonstrated that Mn+2 at 500 mu M, but not the lower doses, increased LHRH release, nitric oxide (NO) synthase (NOS) activity, and the content of cyclic cGMP in the medial basal hypothalamus. Inhibition of NOS with a competitive inhibitor (N omega-nitro-L-arginine methyl ester hydrochloride) prevented the Mn-induced increase in LHRH release. Additionally, methylene blue and KT5823, specific inhibitors of guanylyl cyclase and protein kinase G (PKG), respectively, also blocked the stimulatory effect of Mn+2 on LHRH release. These in vitro studies demonstrated that the hypothalamic mechanism of Mn+2 action in adult males is by activation of the NOS/NO system, resulting in increases in cGMP and PKG and thus the secretion of LHRH from the nerve terminals. These results indicate Mn+2 can cause LHRH release in adult males, and this action is discussed in relation to age, gender, as well as mechanistic and functional differences between adult and immature animals.