%0 Journal Article
%T Influence of ER¦Â selective agonism during the neonatal period on the sexual differentiation of the rat hypothalamic-pituitary-gonadal (HPG) axis
%A Heather B Patisaul
%A Sandra M Losa-Ward
%A Karina L Todd
%A Katherine A McCaffrey
%A Jillian A Mickens
%J Biology of Sex Differences
%D 2012
%I BioMed Central
%R 10.1186/2042-6410-3-2
%X To achieve this, we exposed neonatal female rats to three doses (0.5, 1 and 2 mg/kg) of the ER¦Â selective agonist diarylpropionitrile (DPN) using estradiol benzoate (EB) as a positive control. Measures included day of vaginal opening, estrous cycle quality, GnRH and Fos co-localization following ovariectomy and hormone priming, circulating luteinizing hormone (LH) levels and quantification of hypothalamic kisspeptin immunoreactivity. A second set of females was then neonatally exposed to DPN, the ER¦Á agonist propyl-pyrazole-triol (PPT), DPN+PPT, or EB to compare the impact of ER¦Á and ER¦Â selective agonism on kisspeptin gene expression in pre- and post-pubescent females.All three DPN doses significantly advanced the day of vaginal opening and induced premature anestrus. GnRH and Fos co-labeling, a marker of GnRH activation, following ovariectomy and hormone priming was reduced by approximately half at all doses; the magnitude of which was not as large as with EB or what we have previously observed with the ER¦Á agonist PPT. LH levels were also correspondingly lower, compared to control females. No impact of DPN was observed on the density of kisspeptin immunoreactive (-ir) fibers or cell bodies in the arcuate (ARC) nucleus, and kisspeptin-ir was only significantly reduced by the middle (1 mg/kg) DPN dose in the preoptic region. The second experiment revealed that EB, PPT and the combination of DPN+PPT significantly abrogated preoptic Kiss1 expression at both ages but ARC expression was only reduced by EB.Our results indicate that selective agonism of ER¦Â is not sufficient to completely achieve male-typical HPG organization observed with EB or an ER¦Á agonist.The relative mechanistic roles the two primary forms of the estrogen receptor (ER¦Á and ER¦Â) play in the estrogen-dependent organization of the hypothalamic-pituitary-gonadal (HPG) axis remain incompletely characterized. The present study addressed this data gap by assessing the impact of ER-selective agonism during
%K hypothalamus
%K development
%K sex differences
%K estrogen
%K kisspeptin
%U http://www.bsd-journal.com/content/3/1/2