Adiponectin Regulate Growth Hormone Secretion Via Adiponectin Receptor Mediated Ca²⁺ Signalling in Rat Somatotrophs In Vitro

Abstract

Obesity is associated with reduced levels of growth hormone (GH) and the disruption of pulsatile GH secretion. This results in relative GH deficiency. It is likely that a regulatory relationship between GH secretion and adipose tissue exists as the secretion of GH recovers to normal levels after a reduction in body weight. This report characterise the expression and interaction of adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) and adiponectin, respectively, in regulating the activity of GH secreting cells. Polymerase chain reaction analysis of the GH3 cell line, rat anterior pituitary gland and isolated somatotroph cells from transgenic GFP expressing mice confirmed the expression of both AdipoR1 and AdipoR2 in GH secretory cells. Because GH cells expressed both receptors, it is likely that the measured increase in GH secretion, observed in primary cultured rat pituitary cells after 30 min of incubation with full-length murine adiponectin, was mediated by a direct receptor regulated process. Adiponectin induced an increase in intracellular Ca(2+) through both the influx of extracellular Ca(2+) and the release of intracellular Ca(2+) stores resulting in the secretion of GH. Furthermore, results confirm that this increase in GH secretion depended mainly on an increase in Ca(2+) influx through L-type Ca(2+) channels. It is concluded that adiponectin directly regulates GH secretion from somatotrophs by binding to either adiponectin receptor, and that this is mediated via a similar process observed after the stimulation of GH secretion by GH-releasing hormone.

Adipokine Profile and Urinary Albumin Excretion in Isolated Growth Hormone Deficiency

“…Adiponectin treatment increases GHRH receptor expression in anterior pituitary cell cultures, which suggests a potential indirect regulatory role of adiponectin on GH secretion (32). Therefore, the high adiponectin levels in our model of GHRH resistance could be a compensatory mechanism to the lack of GHRH action.…”

Adiponectin expression in the porcine pituitary during the estrous cycle and its effect on LH and FSH secretion

“…To date, the presence of mRNA for adiponectin and its receptors has only been reported in rats (20,37,44), humans (37), and chickens (35). Adiponectin receptor gene expression was noted in AP and NP of cyclic gilts (19), AP of female rats (20), somatotroph cells isolated from transgenic green fluorescent protein-expressing mice, the GH3 cells (rat pituitary tumor cell line) (44), and L␤T2 (immortalized mouse gonadotrophs) (20,25). Psilopanagioti et al (34) observed the localization of AdipoRs in gonadotrophs, somatotrophs, and thyrotrophs but not in corticotrophs or lactotrophs (34).…”

“…Despite the conflicting evidence on adiponectin's ability to cross the blood-brain barrier (23,32,43), some studies have indicated adiponectin expression in the brain and pituitary of humans, rats, mice, and chickens (5,26,37). The presence of AdipoRs in the human, pig, rat, murine, and chicken hypothalamus and pituitary suggests that adiponectin may be a factor modulating the secretory functions of central branches of hormonal axes and, indirectly, also their peripheral branches, including the HPG axis (19,24,26,34,37,43,44). Rodriguez-Pacheco et al (37) revealed that adiponectin in vitro influences growth hormone and LH secretion by the isolated anterior pituitary cells of rats.…”

Regulated recovery of pulsatile growth hormone secretion from negative feedback: a preclinical investigation

“…The precise factors that mediate these inverse relationships between GH pulsatility and adiposity in humans are not yet known. Potential mechanisms include accentuation of putatively suppressive effects of free fatty acids, IGF-I, insulin, and TNF-␣ and/or attenuation of putatively stimulatory effects of adiponectin, resistin, eucortisolemia, and leptin on GH secretion (24,36,43,54). ApEn provides a model-free and scale-invariant measure of altered feedback control in interlinked systems like the GHRH/ ghrelin/somatostatin/GH axis (14,55).…”