Physiologically Significant Effect of Neuropeptide Y to Suppress Growth Hormone Release by Stimulating Somatostatin Discharge*

Abstract

Neuropeptide Y (NPY) is a peptide found in a variety of hypothalamic loci which is frequently colocalized with catecholamines. It is also secreted into hypophyseal portal vessels. The injection of NPY into the third ventricle (3V) lowered plasma GH levels in conscious, freely moving male rats. To determine the physiological significance of the hypothalamic inhibitory action of the peptide, highly specific antiserum directed against NPY was injected into the 3V of conscious rats. 3V injection of the antiserum evoked a significant elevation of plasma GH within 2 h on comparison to values in normal rabbit serum-injected, ovariectomized rats. The difference increased and reached a maximum at 6 h after injection. On the other hand, there was no effect of the antiserum in ovariectomized, estrogen, progesterone-blocked rats. Intraventricular injection of the anti-NPY serum also caused a significant elevation of plasma GH within 2 h in normal male rats and the increases above values in normal rat serum-injected control animals became even more significant at 3 and 4 h. To determine the mechanism by which NPY lowers GH after its intraventricular injection, its effect on the release of somatostatin (SRIF) from median eminence fragments incubated in vitro was examined. NPY stimulated SRIF release with a highly significant effect at a concentration of 10(-9) M. Borderline stimulation was observed at doses as low as 10(-11) M. The curve was bell-shaped with a declining release at 10(-8) M and 10(-7) M. The releasing action of NPY was blocked by either the alpha 1-receptor blocker, prazosin (10(-6) M), or the beta-receptor blocker, propranolol (10(-6) M), but was not affected by the alpha 2-receptor blocker, yohimbine (10(-6) M). We conclude that NPY has a physiologically significant inhibitory action within the hypothalamus to suppress GH release in ovariectomized female and intact male rats by stimulation of SRIF release by alpha 1 and beta-adrenergic receptor-mediated mechanisms.

Interactions of ghrelin signaling pathways with the GH neuroendocrine axis: a new and experimentally tested model

“…This has been shown by double-labeling experiments for GHS-R and NPY (Willesen et al 1999, Tannenbaum et al 2003, as well as by c-fos expression upon GHS activation in combination with NPY mRNA expression (Dickson & Luckman 1997). Rettori et al (1990) reported that the link between NPY and the suppression of GH in the circulation is mediated by a discharge of SRIF. Injections of NPY led to a suppression of GH lasting, after a delay of about 30-60 min, up to 2 h. They further established a direct link between NPY axons and SRIF neurons by receptor analysis.…”

“…Thus, compared with a previously suggested model (Farhy & Veldhuis 2005), the major novel features of the present model are a) the role played by NPY, a powerful orexigenic hormone, which also stimulates the release of SRIF (Rettori et al 1990), and b) the dissimilar functions of ghrelin in the hypothalamus and in the pituitary. Furthermore, the predictions of this model were experimentally tested and confirmed in the present report.…”

Abnormalities of the somatotrophic axis in the obese agouti mouse

“…In addition, NPY may suppress the somatotrophic axis via stimulation of hypothalamic somatostatin release. 44,45 Hence, the observed reduction in PeVN somatostatin mRNA expression in obese A y /a mice may be secondary to reduced Arc NPY mRNA expression. Since NPY inhibits the growth axis, 20,21 a reduction in Arc NPY would increase circulating GH and hence IGFI levels.…”

Regulation of somatotroph cell function by the adipose tissue

“…This hypothesis is supported by previous data showing that leptin receptors are present in NPY neurones located in the arcuate nucleus of the hypothalamus, as well as immunohistochemical data showing synaptic connections between NPY-connecting neurones and periventricular neurones of the hypothalamus. 16 Further studies looking at the effects of leptin on GH secretion in NPY knock-out mice should help to clarify this possibility. Since we have previously found that leptin inhibits in vitro somatostatin secretion and somatostatin mRNA levels by rat fetal neurones in monolayer culture, 17 it was possible that the stimulatory effect of leptin on GH secretion could be mediated by regulating hypothalamic somatostatin andaor GHRH tone.…”