title: Prenatal alcohol exposure alters response of kisspeptin-ir neurons to estradiol and progesterone in adult female rats.
abstract: BACKGROUND
  Prenatal alcohol exposure (PAE) has adverse effects on reproductive function and hypothalamic-pituitary-gonadal (HPG) activity. Kisspeptin neurons play a role in mediating feedback effects of estradiol (E2 ) and progesterone (P4 ) on the HPG axis. We hypothesized that PAE will have long-term effects on the response of kisspeptin neurons to E2 and P4 .
  
  
  METHODS
  Adult female rats (53 to 58 days) from prenatal ad libitum-fed control (C), pair-fed (PF), and alcohol-exposed (PAE) groups were subjected to Sham ovariectomy (OVX) or OVX without or with replacement with low or high physiological levels of E2 and P4 , and terminated under basal conditions. E2 and P4 levels, and the response of kisspeptin-ir neurons in the arcuate (ARC) and anteroventral periventricular (AVPV) nuclei to these hormones, were measured. As the E2 signal is conveyed to kisspeptin neurons via estrogen receptor-α (ER-α), we investigated PAE effects on the number of kisspeptin-ir/ER-α-ir neurons. To determine whether PAE alters interactions between kisspeptin and gonadotropin-releasing hormone (GnRH) neurons, close contacts between kisspeptin-ir fibers and GnRH-ir cell bodies were examined.
  
  
  RESULTS
  Our data present the novel finding that kisspeptin-ir neurons in the ARC of PAE females show differential responses to E2 and to the combined treatment with E2 and P4 compared with controls: (i) OVX increased the number of kisspeptin-ir neurons in C and PF, but not PAE females compared with their Sham counterparts; (ii) E2 replacement restored kisspeptin-ir cell numbers to Sham levels in C and PF females but caused a robust down-regulation of kisspeptin-ir neurons below Sham levels in PAE females; (iii) OVX and replacement with high physiological concentrations of E2 resulted in fewer kisspeptin-ir cells in PAE than C females; (iv) OVX and replacement with high levels of both E2 and P4 markedly decreased the number of kisspeptin-ir neurons, below levels observed following E2 alone, in PF and C females, but had no significant effect in PAE females.
  
  
  CONCLUSIONS
  These data suggest that a possible mechanism underlying adverse effects of PAE on HPG function involves actions of alcohol on the kisspeptin system.
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada; Laboratory of Neurobiology, Institute of Zoology, Poznań University of Life Sciences, Poznań, Poland.
authors.forename: Joanna H
authors.initials: JH
authors.lastname: Sliwowska
authors.forename: Tamara S
authors.initials: TS
authors.lastname: Bodnar
authors.forename: Joanne
authors.initials: J
authors.lastname: Weinberg
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D059648:Kisspeptins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C491406:Kiss1 protein, rat; D059648:Kisspeptins; D000431:Ethanol; D011374:Progesterone; D004958:Estradiol
keywords: Estrogen; Ethanol; Kisspeptin; Prenatal Alcohol Exposure; Progesterone