Growth hormone-releasing hormone and gonadotropin-releasing hormone stimulate nitric oxide production in 17β-estradiol-primed rat anterior pituitary cells

It was reported that neuronal nitric oxide synthase (nNOS) was expressed only in gonadotrophs and folliculo-stellate cells in the anterior lobe of the pituitary gland. However, recent studies have demonstrated the occurrence of nNOS in the somatotrophs and lactotrophs. In the present study, we investigated effects of growth hormone-releasing hormone (GHRH), gonadotropin-releasing hormone (GnRH), and 17β-estradiol on nitric oxide (NO) release in cultured rat anterior pituitary cells in vitro. The NO2− level in the incubation medium of the rat anterior pituitary cells was dependent on the cell density. Pretreatment with 10 µM 17β-estradiol resulted in an increase in medium NO2− level. GHRH and GnRH failed to change medium NO2− levels, but they elicited increases in medium NO2− levels in estrogen-treated cells. The GHRH-induced increase in NO2− level was inhibited by Nχ-nitro-l-arginine methyl ester, a NOS inhibitor. These findings suggest that GnRH and GHRH could activate nNOS in the gonadotrophs and the somatotrophs, respectively.