Role of nitric oxide in control of prolactin release by the adenohypophysis.

Abstract

Nitric oxide synthase-containing cells were visualized in the anterior pituitary gland by immunocytochemistry. Consequently, we began an evaluation of the possible role of NO in the control of anterior pituitary function.Prolactin is normally under inhibitory hypothalamic control, and in vitro the gland secretes large quantities of the hormone. When hemipituitaries were incubated for 30 min in the presence of sodium nitroprusside, a releaser of NO, prolactin release was inhibited. This suppression was completely blocked by the scavenger of NO, hemoglobin. Analogs of arginine, such as NG-monomethyl-L-arginine (NMMA, where NG is the terminal guanidino nitrogen) and nitroarginine methyl ester, inhibit NO synthase. Incubation of hemipituitaries with either of these compounds significantly increased prolactin release. Since in other tissues most of the actions of NO are mediated by activation of soluble guanylate cyclase with the formation of cyclic GMP, we evaluated the effects of cyclic GMP on prolactin release. Cyclic GMP (10 mM) produced an "40%o reduction in prolactin release. Prolactin release in vivo and in vitro can be stimulated by several peptides, which include vasoactive intestinal polypeptide and substance P. Consequently, we evaluated the possible role of NO in these stimulations by incubating the glands in the presence of either of these peptides alone or in combination with NMMA. In the case of vasoactive intestinal polypeptide, the significant stimulation of prolactin release was augmented by NMMA to give an additive effect. In the case of substance P, there was a smaller but significant release of prolactin that was not significantly augmented by NMMA. We conclude that NO has little effect on the stimulatory action of these two peptides on prolactin release. Dopamine (0.1 ,uM), an inhibitor of prolactin release, reduced prolactin release, and this inhibitory action was significantly blocked by either hemoglobin (20 jig/ml) or NMMA and was completely blocked by 1 mM nitroarginine methyl ester. Atrial natriuretic factor at 1 ,uM also reduced prolactin release, and its action was completely blocked by NMMA. In contrast to these results with prolactin, luteinizing hormone (LH) was measured in the same medium in which the effect of nitroprusside was tested on prolactin release, there was no effect of nitroprusside, hemoglobin, or the combination of nitroprusside and hemoglobin on luteinizing hormone release. Therefore, in contrast to its inhibitory action on prolactin release NO had no effect on luteinizing hormone release. Immunocytochemical studies by others have shown that NO synthase is present in the folliculostellate cells and also the gonadotrophs of the pituitary gland. We conclude that NO produced by either of these cell types may diffuse to the lactotropes, where it can inhibit prolactin release. NO appears to play little role in the The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accorda...

Role of leptin in hypothalamic–pituitary function

“…On the other hand, there was a much more pronounced stimulation of prolactin release at high concentrations, exceeding all induced increases we have observed previously. This was even more remarkable, considering that prolactin release is already augmented from anterior pituitaries in vitro because of removal of inhibitory hypothalamic control (21). We were surprised to see such remarkable increases in gonadotropin release from the incubated pituitaries, which could be of physiologic significance.…”

Contrasting effects of nitric oxide on food intake and GH secretion stimulated by a GH-releasing peptide

“…This view is supported by in vitro studies showing that NOergic neurons play a permissive role in the medial basal hypothalamus to stimulate the release of many regulatory peptides, as corticotrophin-releasing hormone, luteinizing hormone releasing-hormone, GHRH, somatostatin and oxytocin (46). NO, however, has also been reported in some (18,47), though not all (7,48), studies to inhibit GHRH-induced GH release from rat pituitary cell cultures and to affect basal and dopamine inhibition of prolactin secretion (5).…”

Gender Differences and the Effect of Different Endocrine Situations on the NOS Expression Pattern in the Anterior Pituitary Gland

“…When pituitary cells are studied in vitro, data concerning the direct effect of NO on prolactin secretion, like those for LH, are controversial. Some studies propose that it plays an inhibitory role (Duvilanski et al 1995;Vankelecom et al 1997), whereas others suggest a stimulatory role (Brunetti et al 1995;González and Aguilar 1999). Interestingly, the inhibitory effect was particularly apparent in anterior pituitary cultures enriched with FS cells (Vankelecom et al 1997).…”

“…Functional studies suggest that NO may be involved in the secretion of different pituitary hormones (Kato 1992;Brunetti et al 1993;Ceccatelli et al 1993;Duvilanski et al 1995;Rivier 1995;Pinilla et al 1998). The fact that certain endocrine manipulations, such as gonadectomy, produce NOS upregulation in pituitary cells (Ceccatelli et al 1993;Wang et al 1997) also suggests a role for NO in the control of anterior pituitary functions, particularly in the secretion of luteinizing hormone (LH).…”