ArticleBiology of sex differences2012
Influence of ERβ selective agonism during the neonatal period on the sexual differentiation of the rat hypothalamic-pituitary-gonadal (HPG) axis.
Article in Biology of sex differences, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Effects of perinatal bisphenol A exposure on the volume of sexually-dimorphic nuclei of juvenile rats: A CLARITY-BPA consortium study.Neurotoxicology · 2017Article
- Organizational and activational effects of sex steroids on kisspeptin neuron development.Frontiers in neuroendocrinology · 2013Review
- Development and Aging of the Kisspeptin-GPR54 System in the Mammalian Brain: What are the Impacts on Female Reproductive Function?Frontiers in endocrinology · 2013Article
- The development of kisspeptin circuits in the Mammalian brain.Advances in experimental medicine and biology · 2013Review
- Systemic compensatory response to neonatal estradiol exposure does not prevent depletion of the oocyte pool in the rat.PloS one · 2013Article
- Kisspeptin prevention of amyloid-β peptide neurotoxicity in vitro.ACS chemical neuroscience · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIt is well established that sexual differentiation of the rodent hypothalamic-pituitary-gonadal (HPG) axis is principally orchestrated by estrogen during the perinatal period. Here we sought to better characterize the mechanistic role the beta form of the estrogen receptor (ERβ) plays in this process.
methodsTo achieve this, we exposed neonatal female rats to three doses (0.5, 1 and 2 mg/kg) of the ERβ 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 ERα agonist propyl-pyrazole-triol (PPT), DPN+PPT, or EB to compare the impact of ERα and ERβ selective agonism on kisspeptin gene expression in pre- and post-pubescent females.
resultsAll 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 ERα 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.
conclusionOur results indicate that selective agonism of ERβ is not sufficient to completely achieve male-typical HPG organization observed with EB or an ERα agonist.
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