Abstract
The amino acid arginine (Arg) is a recognized secretagogue of growth hormone (GH), and has been shown to induce GH gene expression. Arg is the natural precursor of nitric oxide (NO), which is known to mediate many of the effects of Arg, such as GH secretion. Arg was also shown to increase calcium influx in pituitary cells, which might contribute to its effects on GH secretion. Although the mechanisms involved in the effects of Arg on GH secretion are well established, little is known about them regarding the control of GH gene expression. We investigated whether the NO pathway and/or calcium are involved in the effects of Arg on GH gene expression in rat isolated pituitaries. To this end, pituitaries from approximately 170 male Wistar rats (∼250 g) were removed, divided into two halves, pooled (three hemi-pituitaries) and incubated or not with Arg, as well as with different pharmacological agents. Arg (71 mM), the NO donor sodium nitroprusside (SNP, 1 and 0.1 mM) and a cyclic guanosine monophosphate (cGMP) analogue (8-Br-cGMP, 1 mM) increased GH mRNA expression 60 min later. The NO acceptor hemoglobin (0.3 µM) blunted the effect of SNP, and the combined treatment with Arg and L-NAME (an NO synthase (NOS) inhibitor, 55 mM) abolished the stimulatory effect of Arg on GH gene expression. The calcium channel inhibitor nifedipine (3 µM) also abolished Arg-induced GH gene expression. The present study shows that Arg directly induces GH gene expression in hemi-pituitaries isolated from rats, excluding interference from somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover, the data demonstrate that the NOS/NO signaling pathway and calcium mediate the Arg effects on GH gene expression.
Highlights
Amino acids are essential molecules for protein synthesis, being fundamental for the growth and development of all life forms [1]
It has been pointed out that Arg suppresses the release of somatostatin [4,7,8], which is known to exert an inhibitory effect on insulin and growth hormone (GH) secretion
It can be seen that 7.1 mM Arg did not change GH mRNA content compared to control
Summary
Amino acids are essential molecules for protein synthesis, being fundamental for the growth and development of all life forms [1]. The amino acid L-arginine (Arg) plays a crucial role in nutrition and physiology, as its dietary restriction leads to growth delay. This event does not seem to be associated with the primary function of amino acids as building blocks for proteins, since the restriction of some other amino acids does not interfere with this process, a fact that reinforces the importance of Arg for growth [2]. It has been pointed out that Arg suppresses the release of somatostatin [4,7,8], which is known to exert an inhibitory effect on insulin and GH secretion. Arg treatment increased calcium influx in pancreatic beta and pituitary cells in culture, suggesting a stimulatory effect on the secretion of insulin and GH [9,10,11]
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