Central Kisspeptin Does Not Affect ERK1/2 or p38 Phosphorylation in Oxytocin Neurons of Late-Pregnant Rats

Abstract

Oxytocin is secreted by hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) oxytocin neurons to induce uterine contractions during parturition. Increased activation of oxytocin neurons at parturition involves a network of afferent inputs that increase oxytocin neuron excitability. Kisspeptin fibre density increases around oxytocin neurons during pregnancy, and central kisspeptin administration excites oxytocin neurons only in late pregnancy. Kisspeptin signals via extracellular regulated kinase 1/2 (ERK1/2) and p38. Therefore, to determine whether kisspeptin excites oxytocin neurons via ERK1/2-p38 signalling in late-pregnant rats, we performed immunohistochemistry for phosphorylated ERK1/2 (pERK1/2) and phosphorylated p38 (p-p38) in oxytocin neurons of non-pregnant and late-pregnant rats. Intracerebroventricular (ICV) kisspeptin administration (2 µg) did not affect pERK1/2 or p-p38 expression in SON and PVN oxytocin neurons of non-pregnant or late-pregnant rats. Furthermore, ICV kisspeptin did not affect pERK1/2 or p-p38 expression in brain areas with major projections to the SON and PVN: the nucleus tractus solitarius, rostral ventrolateral medulla, locus coeruleus, dorsal raphe nucleus, organum vasculosum of the lamina terminalis, median preoptic nucleus, subfornical organ, anteroventral periventricular nucleus, periventricular nucleus and arcuate nucleus. Hence, kisspeptin-induced excitation of oxytocin neurons in late pregnancy does not appear to involve ERK1/2 or p38 activation in oxytocin neurons or their afferent inputs.

Kisspeptin neuron projections to oxytocin neurons are not necessary for parturition in the mouse

“…In rats, kisspeptin neuron projections to the SON originate from the PeN and kisspeptin fiber density around the SON is maximal in late pregnancy (Seymour et al 2017 ; Augustine et al 2018 ). While intravenous kisspeptin excites rat oxytocin neurons across pregnancy and lactation by activation of vagal afferents (Scott and Brown 2011 , 2013 ), central kisspeptin excitation of rat oxytocin neurons emerges over pregnancy to a maximum in late pregnancy (Augustine et al 2018 ), and is mediated by a local action within the SON (Abbasi et al 2022b ) that does not involve activation of the canonical kisspeptin signaling pathway in oxytocin neurons (Abbasi et al 2022a ). Hence, it appears that kisspeptin neurons specifically excite oxytocin neurons in late-pregnant rats.…”