Developmental changes in the mammalian gonadotropin-inhibitory hormone (GnIH) ortholog RFamide-related peptide (RFRP) and its cognate receptor GPR147 in the rat hypothalamus

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• 作者：Takeshi Iwasa^a ; ^{takeshi1@clin.med.tokushima-u.ac.jp} ; Toshiya Matsuzaki^a ; Masahiro Murakami^a ; Riyo Kinouchi^a ; Tomohiro Osugi^b ; Ganbat Gereltsetseg^a ; Shinobu Yoshida^a ; Minoru Irahara^a ; Kazuyoshi Tsutsui^b
• 关键词：Gonadotropins ; Gonadotropin-inhibitory hormone (GnIH) ; RFamide-related peptide (RFRP) ; G protein-coupled receptor 147 (GPR147) ; Hypothalamus ; Development
• 刊名：International Journal of Developmental Neuroscience
• 出版年：2012
• 出版时间：February 2012
• 年：2012
• 卷：30
• 期：1
• 页码：31-37
• 全文大小：455 K

文摘

The mammalian gonadotropin-inhibitory hormone (GnIH) ortholog RFamide-related peptide (RFRP) is considered to act on gonadotropin-releasing hormone (GnRH) neurons and on the pituitary to inhibit gonadotropin release and synthesis. To understand the functional significance of this neuropeptide, we investigated the physiological changes in RFRP at mRNA and peptide levels, as well as at the mRNA level of its cognate receptor, G protein-coupled receptor 147 (<em>GPR147em>), in the rat hypothalamus during development. We also investigated the effects of gonadal steroids on mRNA expression levels of these molecules. In male rats, mRNA expressions of both <em>RFRPem> and <em>GPR147em> increased from postnatal days 12 and 16, peaking at postnatal days 35 and 42, respectively. However, their expressions fell at postnatal day 49. In female rats, mRNA expression of <em>RFRPem> continued to increase throughout development; mRNA expression of <em>GPR147em> in female rats increased from postnatal day 16, peaking at postnatal day 28, but decreased from postnatal day 35. The hypothalamic contents of RFRP on postnatal days 28 and 42 were significantly higher than on postnatal day 4 in male rats, and those on postnatal day 42 were significantly higher than those on postnatal days 4 and 28 in females. Neither orchidectomy nor ovariectomy influenced mRNA expression levels of <em>RFRPem> or <em>GPR147em> in the prepubertal period when endogenous sex steroid levels were low in males and females. Administration of estradiol-17¦Â (E2) increased mRNA expression of <em>RFRPem> in prepubertal females. These results suggest that the hypothalamic RFRP system changes during development. An ovarian sex steroid, E2, may stimulate mRNA expression of <em>RFRPem> in the prepubertal period when the basal E2 concentration is low.