title: Neonatal exposure to 17β-estradiol down-regulates the expression of synaptogenesis related genes in selected brain regions of adult female rats.
abstract: OBJECTIVE
  Administration of estradiol or compounds with estrogenic activity to newborn female rats results in irreversible masculinization as well as defeminization in the brain and the animals exhibit altered reproductive behavior as adults. The cellular and molecular mechanism involved in inducing the irreversible changes is largely unknown. In the present study, we have monitored the changes in the expression of selected synaptogenesis related genes in the sexually dimorphic brain regions such as POA, hypothalamus and pituitary following 17β-estradiol administration to neonatal female rats.
  
  
  METHODS
  Female Wistar rats which were administered 17β-estradiol on day 2 and 3 after birth were sacrificed 120days later and the expression levels of genes implicated in synaptogenesis were monitored by semi-quantitative reverse transcription PCR. Since estradiol induced up-regulation of COX-2 in POA is a marker for estradiol induced masculinization as well as defeminization, in the present study only animals in which the increase in expression of COX-2 gene was observed in POA were included in the study.
  
  
  RESULTS
  Down-regulation of genes such as NMDA-2B, NETRIN-1, BDNF, MT-5 MMP and TNF-α was observed in the pre-optic area of neonatally E2 treated female rat brain but not in hypothalamus and pituitary compared to the vehicle- treated controls as assessed by RT-PCR and Western blot analysis.
  
  
  CONCLUSIONS
  Our results suggest a possibility that down-regulation of genes associated with synaptogenesis in POA, may be resulting in disruption of the cyclical regulation of hormone secretion by pituitary the consequence of which could be infertility and altered reproductive behavior.
authors.affiliation: Department of Microbiology and Biotechnology, Bangalore University, Bangalore, India.
authors.forename: N S
authors.initials: NS
authors.lastname: Radhika
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore, India.
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Govindaraj
authors.affiliation: Department of Microbiology and Biotechnology, Bangalore University, Bangalore, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Sarangi
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore, India. Electronic address: ajrao@biochem.iisc.ernet.in.
authors.forename: A J
authors.initials: AJ
authors.lastname: Rao
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005262:Feminization; D015870:Gene Expression / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000254:growth & development; D008297:Male; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics*; D010902:Pituitary Gland / Q000187:drug effects / Q000254:growth & development; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011301:Preoptic Area / Q000187:drug effects / Q000254:growth & development; D051381:Rats; D012733:Sex Differentiation / Q000187:drug effects; D013569:Synapses / Q000187:drug effects*
chemical_list: D004967:Estrogens; D004958:Estradiol; D051546:Cyclooxygenase 2
keywords: Hypothalamus; Neonatal 17β-estradiol exposure; Pituitary; Pre-optic area; Synaptogenesis