title: The Inhibitory Effects of RFamide-Related Peptide 3 on Luteinizing Hormone Release Involves an Estradiol-Dependent Manner in Prepubertal but Not in Adult Female Mice.
abstract: The mammalian gonadotropin-inhibitory hormone (GnIH) ortholog, RFamide-related peptide (RFRP), is considered to act on gonadotropin-releasing hormone (GnRH) neurons and the pituitary to inhibit gonadotropin synthesis and release. However, there is little evidence documenting whether RFamide-related peptide 3 (RFRP-3) plays a primary role in inhibition of the hypothalamo-pituitary-gonadal (HPG) axis prior to the onset of puberty. The present study aimed to understand the functional significance of the neuropeptide on pubertal development. The developmental changes in reproductive-related gene expression at the mRNA level were investigated in the hypothalamus of female mice. The results indicated that RFRP-3 may be an endogenous inhibitory factor for the activation of the HPG axis prior to the onset of puberty. In addition, centrally administered RFRP-3 significantly suppressed plasma luteinizing hormone (LH) levels in prepubertal female mice. Surprisingly, centrally administered RFRP-3 had no effects on plasma LH levels in ovariectomized (OVX) prepubescent female mice. In contrast, RFRP-3 also inhibited plasma LH levels in OVX prepubescent female mice that were treated with 17beta-estradiol replacement. Our study also examined the effects of RFRP-3 on plasma LH release in adult female mice that were ovariectomized at dioestrus, with or without estradiol (E2). Our results showed that the inhibitory effects of RFRP-3 were independent of E2 status. Quantitative real-time PCR and immunohistochemistry analyses showed that RFRP-3 inhibited GnRH expression at both the mRNA and protein levels in the hypothalamus. These data demonstrated that RFRP-3 could effectively suppress pituitary LH release, via the inhibition of GnRH transcription and translation in prepubescent female mice, which is associated with estrogen signaling pathway and developmental stages.
authors.affiliation: College of Bioengineering, Chongqing University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiang
authors.affiliation: College of Bioengineering, Chongqing University, Chongqing, China.
authors.forename: Baoyun
authors.initials: B
authors.lastname: Zhang
authors.affiliation: College of Bioengineering, Chongqing University, Chongqing, China.
authors.forename: Fenglin
authors.initials: F
authors.lastname: Lv
authors.affiliation: College of Bioengineering, Chongqing University, Chongqing, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Ma
authors.affiliation: College of Bioengineering, Chongqing University, Chongqing, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Chen
authors.affiliation: College of Bioengineering, Chongqing University, Chongqing, China.
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.affiliation: College of Bioengineering, Chongqing University, Chongqing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: College of Bioengineering, Chongqing University, Chongqing, China wang_pq@21cn.com.
authors.forename: Pingqing
authors.initials: P
authors.lastname: Wang
authors.affiliation: Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Chu
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000096:biosynthesis; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051379:Mice; D009479:Neuropeptides / Q000494:pharmacology*; D010052:Ovariectomy; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D012741:Sexual Maturation / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D009479:Neuropeptides; C416987:RFamide peptide; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone
keywords: development; gonadotropin-inhibitory hormone; hypothalamic hormones; luteinizing hormone; steroid hormones