Abstract
BackgroundGonadotropin-releasing hormone (GnRH) and kisspeptin in the hypothalamus are thought to be crucial components of the hypothalamic-pituitary-gonadal (HPG) axis and maintain reproductive function. These neuropeptides are also expressed in the placenta, where they may contribute to placental physiology. In this study, we examined how these peptides are regulated within the placenta.MethodsWe used primary cultures of placental tissue from rats of 16–18 days gestation. After stimulation with estradiol, GnRH, kisspeptin, and neurokinin B (NKB), changes in placental GnRH, kisspeptin, and human chorionic gonadotropin (hCG) mRNA expression were evaluated by real-time quantitative RT-PCR analysis.ResultsImmunocytochemical analysis showed that rat placental cells contained cells expressing kisspeptin or GnRH. GnRH and kisspeptin mRNA expression was significantly increased in placental cells in the presence of estradiol; NKB mRNA expression was also stimulated by estradiol. Stimulation of the cells with kisspeptin failed to stimulate GnRH mRNA expression. Conversely, both GnRH itself and NKB increased GnRH mRNA expression. Kisspeptin mRNA expression was not increased by kisspeptin itself; however, GnRH and NKB significantly increased kisspeptin mRNA expression. hCG expression was increased in the presence of estradiol. In addition, kisspeptin, GnRH, and NKB could stimulate the expression of hCG mRNA in placental cells.ConclusionsOur experiments using primary cultures of rat placental cells showed that GnRH, kisspeptin, and NKB expression was enhanced by estradiol, and unlike in the hypothalamus, kisspeptin did not control the expression of GnRH in placental cells. NKB might be located upstream of kisspeptin and GnRH, and these neuropeptides might be involved in the induction of hCG expression in placental cells.
Highlights
Gonadotropin-releasing hormone (GnRH) and kisspeptin in the hypothalamus are thought to be crucial components of the hypothalamic-pituitary-gonadal (HPG) axis and maintain reproductive function
GnRH and kisspeptin expression in rat placental cells Primary cultures of rat placental cells collected from rats of 16–18 days gestation were cultured
Effect of estradiol on GnRH, kisspeptin, and neurokinin B (NKB) mRNA expression We examined whether GnRH and kisspeptin, which are expressed in placental cells, were regulated by estradiol
Summary
Gonadotropin-releasing hormone (GnRH) and kisspeptin in the hypothalamus are thought to be crucial components of the hypothalamic-pituitary-gonadal (HPG) axis and maintain reproductive function. These neuropeptides are expressed in the placenta, where they may contribute to placental physiology. After the discovery of inactivating mutations in the kisspeptin receptor of patients with idiopathic hypogonadotropic hypogonadism [1, 2], hypothalamic kisspeptin is defined to be located upstream of gonadotropinreleasing hormone (GnRH)-expressing neurons and accepted as a crucial regulator of the hypothalamicpituitary-gonadal (HPG) axis. GnRH has been detected in extravillous cytotrophoblasts in human placenta during the 1st trimester [7], and the existence of GnRH receptors in these cells was reported [8].
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