Stimulation of growth hormone by kisspeptin antagonists in ewes

Abstract

Kisspeptin signalling is indispensable for fertility, stimulating gonadotropin-releasing hormone (GnRH) secretion and mediating gonadal steroid feedback on GnRH neurons. Moreover, kisspeptin neurons have been implicated in other non-reproductive neuroendocrine roles. Kisspeptin appears to also regulate growth hormone secretion but much of the data appear contradictory. We sought to clarify a potential role of kisspeptin in growth hormone (GH) regulation by examining the effect of kisspeptin antagonists on GH secretion in ewes under various physiological conditions. Our data show clear and robust increases in GH secretion following lateral ventricle or third ventricle infusion of kisspeptin antagonists p-234 and p-271 in either ovariectomized or anestrous ewes. Central infusion of kisspeptin-10 had no effect on GH secretion. To determine the level at which kisspeptin may influence GH secretion, we examined expression of the cognate kisspeptin receptor, GPR54, in pituitary cells and showed by immunocytochemistry that the majority of somatotropes express GPR54 while expression was largely negative in other pituitary cells. Overall, we have demonstrated that blocking kisspeptin signalling by antagonists stimulates GH secretion in ewes and that this is likely mediated by inhibiting endogenous kisspeptin activation of GPR54 expressed on somatotropes. The findings suggest that endogenous kisspeptin inhibits GH secretion through GPR54 expressed on somatotropes.

ERα Signaling in GHRH/Kiss1 Dual-Phenotype Neurons Plays Sex-Specific Roles in Growth and Puberty

“…Because gonadal steroids synthesis continues and Ghrh and Kiss1 coexpression is negligible, we predict that a switch in the pattern of GHRH-Kiss1 expression and secretion is established during pubertal transition. In support of this concept are the studies showing that kisspeptins restrain GH release independent of direct GH feedback actions (Whitlock et al, 2010;Smith et al, 2018;Bohlen et al, 2019;Silveira et al, 2019). Thus, the increase of kisspeptin in detriment of GHRH release would be expected to decrease GH secretion and potentially stimulate the gonadotropic axis.…”

Kisspeptin-10 Promoting the Synthesis of Milk Fat by Inhibiting the AMPK/SIRT6 Signaling Pathway via the GPR54 in Bovine Mammary Epithelial Cells

“…Kisspeptin-10 (Kp-10) is a peptide hormone encoded by kiss 1 gene, which is synthesized by hydropthalamic neurons and play a variety of biological functions in the body through its receptor GPR54 [16]. Meanwhile, GPR54 regulates the release of GnRH and inhibits the synthesis of growth hormone [17,18]. Knockout of GPR54 inhibits mammary gland and ovarian development in puberty mice [19].…”