On the role of the peptide galanin in regulation of growth hormone secretion

Abstract

The effects of the peptide galanin on growth hormone secretion were studied in vitro using cultured rat and human anterior pituitary cells, and in vivo by iv administration of galanin in both rats and humans. Galanin in concentrations from 10 nmol/l to 1 \g=m\mol/ldid not alter basal GH release, but slightly inhibited GHRH-stimulated GH release from cultured rat anterior pituitary cells. Galanin (1 \g=m\mol/l)did not significantly change basal or GHRH-stimulated GH secretion from cultured human anterior pituitary cells. In contrast, iv injection of 1 \ g=m\ g (300 pmol) galanin to rats induced an increase in plasma GH that was reproducible at repetitive injections. The galanin-induced GH release in rats was of a lower magnitude than the increase in plasma GH after iv injections of GHRH, and was seen with a 5-15 min delay in comparison to iv administered GHRH. In man, iv infusions of galanin (40 pmol \ m=. \ kg\ m=-\ 1 \ m=. \min\m=-\1\ m=. \(40 min)) also caused a significant increase in plasma GH, but it occurred 25-30 min after the beginning of the infusion. These results suggest an indirect action of galanin on GH release in both ratsand humans, i.e. galanin does not directly affect the somatotropes. In agreement with a central action, no binding sites for galanin could be demonstrated in the rat anterior pituitary by autoradiography. Since galanin did not affect somatostatin release from fragments of rat mediobasal hypothalamus, the stimulatory effects ofg a l a n i n on GH release are most likely mediated via a stimulatory effect on GHRH neurons.Galanin is a 29 amino acid peptide, initially isolated from porcine small intestine (1), with little struc¬ tural similarity to other known peptides (2). Galanin-like immunoreactivity is widely distributed in the central and peripheral nervous system (2-5). In the brain, the hypothalamus is particularly rich in cell bodies and fibres containing galanin-like im¬ munoreactivity (3,4), with the highest concentration of galanin-like immunoreactivity in the median eminence (5). Specific binding sites for ga¬ lanin have also been demonstrated in the mediobasal hypothalamus (6-9). Taken together, these observations suggest that galanin has a role in reg¬ ulating anterior pituitary function.Galanin has been reported to elicit increased plasma GH levels in rats when given intracerebroventricularly (icv) (6,10-13), sc (14) and iv (11,13). It has also been reported that iv infusion of galanin raises plasma GH levels in humans (15-17). The role of galanin at the rat pituitary level is, however, unclear. Some authors have observed a direct sti¬ mulatory effect of galanin on GH secretion (18,19), but others have failed to demonstrate any effect on basal GH release from dispersed rat anterior pitu¬ itary cells (10,11,20,21). Both inhibitory (19,20) and stimulatory (18) effects of galanin on GHRHstimulated GH secretion have been reported. In crude membrane preparations from the porcine anterior pituitary (22), no galanin binding sites have been demonstrated, pointing at a predomi¬ n...

Effects of Ovine Corticotropin-Releasing Hormone Injection and Desmopressin Coadministration on Galanin and Adrenocorticotropin Plasma Levels in Normal Women

“…Earlier binding studies (20,21), while detecting specific binding sites in the brain, have failed to demonstrate GAL receptors in the anterior pituitary. Our recent data (unpublished observations) have shown that no significant changes in circulating GAL levels occur after TRH, GnRH, and GHRH injections in man, further suggesting that GAL is probably not secreted from the pituitary gland in response to stimulations with hypothalamic releasing peptides.…”

Neuropeptides in anterior pituitary development

“…The regulation of proliferation and of lactotroph secretory activity by galanin has been confirmed by studies on animals using genetic alterations of the galanin gene (Wynick et al, 1998b). Relationships have also been reported with secretion of LH (Lopez et al, 1991(Lopez et al, , 1993Sahu et al, 1994;Arvat et al, 1995;Giustina et al, 1995;Xu et al, 1996;Elsaesser, 2001;Todd et al, 1998), GH (mainly in man, where the human form of galanin (hGAL) is a 30-amino acid peptide) (Carey et al, 1993;Chan et al, 1996;Cremagnani et al, 1996;Davis et al, 1987;Gabriel et al, 1988;Giustina et al, 1993Giustina et al, , 1994Giustina et al, , 1995Hulting et al, 1991;Loche et al, 1989;Maiter et al, 1990;Moore et al, 1994;Murakami et al, 1989;Nishiki et al, 1997;Ottlecz et al, 1986;Sato et al, 1991;Spencer et al, 1994;Todd et al, 2000), and ACTH (Cimini et al, 1993;Cimini, 1996;Hooi et al, 1990b;Malendowicz et al, 1994c).…”

Hypothalamic Regulation of Anterior Pituitary Function

“…Both central and peripheral galanin administration induce GH secretion and potentiate GHRH-stimulated GH secretion [108]. In humans, galanin caused a significant increase in plasma GH through both direct GHRH stimulation [109] and somatostatin inhibition [108]. Interestingly, galanin mRNA expression in GHRH neurons is also considerably higher in males than females [108], suggesting that sexually dimorphic GH pulsatility may be related to galanin expression.…”