Developmental changes in the content of oestrogen receptors in the hypothalamus of the female rat.
Ontology highlight
ABSTRACT:
SUBMITTER: White JO
PROVIDER: S-EPMC1161784 | biostudies-other | 1979 Nov
REPOSITORIES: biostudies-other
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Project description:The onset of puberty is the result of an increase in secretion of hypothalamic gonadotrophin-releasing hormone (GnRH). This action is a result of not only the development of stimulatory inputs to its release, but also the gradual decrease in inhibitory inputs that restrain release of the peptide prior to pubertal onset. Dynorphin (DYN) is one of the inhibitory inputs produced in the medial basal hypothalamus (MBH); however, little is known about what substance(s) control its prepubertal synthesis and release. Because neurokinin B (NKB) increases in the hypothalamus as puberty approaches, we considered it a candidate for such a role. An initial study investigated the acute effects of an NKB agonist, senktide, on the secretion of DYN from MBH tissues incubated in vitro. In other experiments, central injections of senktide were administered to animals for 4 days then MBHs were collected for assessment of DYN synthesis or for the in vitro secretion of both DYN and GnRH. Because insulin-like growth factor (IGF)-1 has been shown to play an important role at puberty, additional animals received central injections of this peptide for 4 days to assess NKB and DYN synthesis or the in vitro secretion of NKB. The results obtained show that senktide administration up-regulates the NKB receptor protein, at the same time as suppressing the DYN and its receptor. Senktide consistently suppressed DYN and elevated GnRH secretion in the same tissue incubates from both the acute and chronic studies. IGF-1 administration caused an increase in NKB protein, at the same time as decreasing DYN protein. Furthermore, the central administration of IGF-1 caused an increase in NKB release, an action blocked by the IGF-1 receptor blocker, JB-1. These results indicate that the IGF-1/NKB pathway contributes to suppressing the DYN inhibitory tone on prepubertal GnRH secretion and thus facilitates the puberty-related increase in the release of GnRH to accelerate the onset of puberty.
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Project description:To determine the global changes in hypothalamic gene expression that may occur at the time of female puberty in this species, animals were euthanized at three different stages, juvenile (25-days of age), early puberty (30-35 days of age) and on the day of the first proestrus (32-37 days of age). According to criteria previously established (Ojeda,S.R.; Urbanski,H.F. Puberty in the rat pp.363-409. The Physiology of Reproduction, 2nd Edition, Vol 2. Edited by Knobil,E.; Neill,J.D. Raven Press, 1994), 25-day-old animals are in the mid- juvenile phase of prepubertal development (JUV). At this time, the vagina is not yet patent and the uterine weight is 60Â mg or less, with no accumulation of intrauterine fluid. Older rats showing a closed vagina, accumulation of intrauterine fluid and an uterine weight less that 180 mg are considered to be in the early proestrous (EP) phase of puberty. Finally, rats still exhibiting a closed vagina, but showing a uterus ballooned with fluid and a uterine weight of at least 200Â mg are considered to be in late proestrus (LP), i.e., the phase of puberty when the first preovulatory surge of LHRH and gonadotropins takes place. The first ovulation occurs the following day. All animals were sacrificed between 1600-1700 h, and the medial basal hypothalamus (MBH) was immediately dissected, as previously described (Rogers,L.C.; Junier,M-P.; Farmer,S.R.; Ojeda,S.R. A sex-related difference in the developmental expression of class II -tubulin messenger RNA in rat hypothalamus. Mol.Cell.Neurosci., 2: 130-138, 1991) and stored in RNAlater according to manufacturerâs instructions. Experiment Overall Design: Affymetrix arrays were used to detect global changes in gene expression in the hypothalamus of normal sexual development of the female rat.
2008-06-16 | E-GEOD-8310 | biostudies-arrayexpress