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.
Highlights
It is well established that sexual differentiation of the rodent hypothalamic-pituitary-gonadal (HPG) axis is principally orchestrated by estrogen during the perinatal period
We have shown that neonatal administration of estradiol benzoate (EB) significantly reduces Kiss-ir in the female rat ARC suggesting that estrogen plays an important role in organizing this sex difference
Co-localization of gonadotropin releasing hormone (GnRH) and Fos in the organum vasculosum of the lamina terminalis (OVLT) GnRH activation in response to the sequential administration of EB and progesterone was assessed by quantifying the percent of GnRH and Fos co-labeling
Summary
It is well established that sexual differentiation of the rodent hypothalamic-pituitary-gonadal (HPG) axis is principally orchestrated by estrogen during the perinatal period. We sought to better characterize the mechanistic role the beta form of the estrogen receptor (ERb) plays in this process. The relative mechanistic roles the two primary forms of the estrogen receptor (ERa and ERb) play in the estrogendependent organization of the hypothalamic-pituitarygonadal (HPG) axis remain incompletely characterized. GnRH secretion is regulated by positive and negative steroid feedback loops. These hormone sensitive, neuroendocrine pathways are sexually dimorphic and organized, primarily, by hormones in a series of perinatal critical periods. Neonatal estrogen administration can defeminize the female hypothalamus resulting in the inability to generate a GnRH surge in adulthood [3]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
