Aging reduces kisspeptin receptor (GPR54) expression levels in the hypothalamus and extra‑hypothalamic brain regions

Abstract

Aging leads to the diminished pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH). Kisspeptin (Kp), the upstream regulator of the hypothalamic-pituitary-gonadal (HPG) axis, regulates GnRH synthesis and release through its cognate receptor, G-protein coupled receptor 54 (GPR54). In turn, GnRH regulates GPR54 expression. GnRH administration into the third ventricle has been shown to induce neurogenesis in different brain regions in old age. However, aging-associated changes in hypothalamic and extra-hypothalamic GPR54 expression were unclear. Therefore, the expression levels of GPR54 were evaluated in various brain regions of adult (age, 3-4 months) and old (age, 20-24 months) male Wistar rats in the present study. In the hypothalamus, mRNA and protein levels of Kp and GPR54 were identified to be significantly decreased in old age. Furthermore, GnRH1 expression in the hypothalamus was analyzed to observe the functional consequence of a reduced Kp-GPR54 system in the hypothalamus. It was found that hypothalamic GnRH1 levels were significantly decreased in old age. As GnRH regulates GPR54 levels, GPR54 was examined in extra-hypothalamic regions. GPR54 levels were found to be significantly decreased in the hippocampus and medulla and pons in old-age rats when compared to adult rats. Notably, GPR54 expression was observed in the frontal lobe, cortex, midbrain and cerebellum of adult and old-age rats; however, the difference between the two groups was not statistically significant. To the best of our knowledge, this is the first study that provides the quantitative distribution of GPR54 in different brain regions during aging. Thus, the reduced levels of Kp and its receptor, GPR54 in the hypothalamus could be cumulatively responsible for reduced levels of GnRH observed in old age.

Serum kisspeptin and proopiomelanocortin in cystic fibrosis: a single study

“…KISS was negatively correlated with age, BMI, CRP, and serum leptin level among participants with CF. Serum KISS levels of healthy women were found to be significantly and negatively correlated with age (R = − 0.458) in the study by Erel et al 43 Declined levels of KISS and its receptor in different brain regions with age were also observed in animal studies 44 . Sitticharoon et al revealed that serum KISS was positively correlated with body weight, BMI, and serum leptin in male subjects 31 .…”

«he Always Talked About Something Else…» Alexey Matveyevich Olovnikov and His Unusual Science

“…В исследовании на крысах разного возраста было показано, что экспрессия GPR54 (аналог KISS1R у крыс) и КП в гипоталамусе значительно снижается при старении. Авторы предполагают, что снижение уровня КП и его рецептора GPR54 в гипоталамусе может быть ответственным за снижение уровня ГнРГ, наблюдаемое в пожилом возрасте [30]. Кроме того, показано, что КП выполняют роль трансмиттеров в передаче сигналов от половых гормонов (эстрогенов, андрогенов), а также осуществляют посреднические функции между лептином и ГнРГ-секретирующими центрами гипоталамуса, в результате осуществляя процессы «прямой/обратной связи» в пределах гонадной оси и сигнализируя об энергетическом балансе в названные центры [39].…”

“…Репродуктивное старение, в частности старение яичников, у человека остается малоизученным. Многими исследователями показано, что репродуктивное старение характеризуется снижением экспрессии КП в гипоталамусе [27,30]. С другой стороны, женщины со сниженным овариальным резервом имеют значительное увеличение симпатических нервных волокон в яичниках, стимуляция которых β-адреномиметиками индуцирует экспрессию КП яичниками [31].…”

Sexual Dimorphism in Kisspeptin Signaling

“…In ageing rats, the number of KNDy neurons are reduced, resulting in a reduced level of pulsatile secretion of GnRH [ 64 ]. Both mRNA and protein levels of KPs and KPR are significantly decreased in the hypothalamus of ageing rats [ 112 ]. However, changes in the numbers of KP neurons and level of KP expression in humans differs from their rodent counterparts [ 113 ].…”