title: Corticotrophin-releasing factor alters the timing of puberty in the female rat.
abstract: Puberty is a developmental process that is dependent upon activation of the hypothalamic gonadotrophin-releasing hormone (GnRH) pulse generator. It is well established that the stress neuropeptide, corticotrophin-releasing factor (CRF), has a profound inhibitory action on GnRH pulse generator frequency. Although stress is known to affect the timing of puberty, the role of CRF is unknown. The present study aimed to test the hypothesis that CRF plays a critical role in the timing of puberty. On postnatal day (pnd) 28, female rat pups were chronically implanted with i.c.v. cannulae and received 14 days of administration of either CRF, CRF receptor antagonist (astressin-B) or artificial cerebrospinal fluid via an osmotic mini-pump. A separate group of rats served as nonsurgical controls. As a marker of puberty, rats were monitored for vaginal opening and first vaginal oestrus. Levels of CRF, CRF receptor types 1 and 2 (CRF-R1, CRF-R2) mRNA expression in micropunches of the medial preoptic area (mPOA), hypothalamic paraventricular nucleus (PVN) and arcuate nucleus (ARC) were determined across pubertal development; brain tissue was collected from a naive group of rats on pnd 14, 32, on the day of vaginal opening, and pnd 77 (Adult). Administration of CRF resulted in a delay in the onset of puberty, whereas astressin-B advanced pubertal onset. Additionally, CRF and CRF-R1 mRNA expression was reduced in the mPOA, but not ARC, at puberty. In the PVN, expression of CRF, but not CRF-R1 mRNA, was reduced at the time of puberty. These data support the hypothesis that CRF signalling may play an important role in modulating the timing of puberty in the rat.
authors.affiliation: Division of Reproduction & Endocrinology, King's College London, Guy's Campus, London, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Kinsey-Jones
authors.forename: X F
authors.initials: XF
authors.lastname: Li
authors.forename: A M I
authors.initials: AM
authors.lastname: Knox
authors.forename: Y S
authors.initials: YS
authors.lastname: Lin
authors.forename: S R
authors.initials: SR
authors.lastname: Milligan
authors.forename: S L
authors.initials: SL
authors.lastname: Lightman
authors.forename: K T
authors.initials: KT
authors.lastname: O'Byrne
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D002404:Catheterization; D002491:Central Nervous System Agents / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D004971:Estrus / Q000378:metabolism; D005260:Female; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011301:Preoptic Area / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D012741:Sexual Maturation / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014621:Vagina / Q000502:physiology; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D002491:Central Nervous System Agents; D010446:Peptide Fragments; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; C120841:astressin B; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone