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“It

is well established that estrogen administration during neonatal development can advance pubertal onset and prevent the maintenance of regular estrous cycles in female rats. This treatment paradigm also eliminates the preovulatory rise of gonadotropin releasing hormone (GnRH). It remains unclear, however, through which of the two primary forms of the estrogen receptor (ER alpha or ER beta) this effect is mediated. It is also unclear whether endocrine disrupting compounds (EDCs) Selleckchem LY333531 can produce similar effects. Here we compared the effect of neonatal exposure to estradiol benzoate (EB), the ER alpha specific agonist 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT), the ER beta specific agonist diarylpropionitrile (DPN) and the naturally occurring EDCs genistein (GEN) and equol (EQ) on pubertal onset, estrous QNZ supplier cyclicity, GnRH activation, and kisspeptin content in the anteroventral periventricular

(AVPV) and arcuate (ARC) nuclei. Vaginal opening was significantly advanced by EB and GEN. By 10 weeks post-puberty, irregular estrous cycles were observed in all groups except the control group. GnRH activation, as measured by the percentage of immunopositive GnRH neurons that were also immunopositive for Fos, was significantly lower in all treatment groups except the DPN group compared to the control group. GnRH activation was absent in the PIT group. These data suggest that neonatal exposure to EDCs can suppress GnRH 2-hydroxyphytanoyl-CoA lyase activity in adulthood, and that ER alpha plays a pivotal role in this process. Kisspeptins (KISS) have recently been characterized to be potent stimulators of GnRH secretion.

Therefore we quantified the density of KISS immunolabeled fibers in the AVPV and ARC. In the AVPV, KISS fiber density was significantly lower in the EB and GEN groups compared to the control group but only in the EB and PPT groups in the ARC. The data suggest that decreased stimulation of GnRH neurons by KISS could be a mechanism by which EDCs can impair female reproductive function. (c) 2008 Elsevier Inc. All rights reserved.”
“It has been postulated that dihydroxyphenylacetic acid (DOPAC), a major dopamine metabolite, and nitric oxide ((center dot)NO) induce mitochondrial dysfunction in a synergistic manner. We examined the combined effects of (center dot)NO and DOPAC on PC-12 cells in terms of cell viability, nuclear morphology, mitochondrial parameters and cell death mechanisms. The apoptotic cell death induced by the (center dot)NO-donor, S-nitroso-N-acetylpenicillamine (SNAP), was differently modulated by DOPAC as a function of DOPAC/cell ratios. Whereas below 200 nmol/10(6) cells, DOPAC inhibited a typical apoptotic pathway induced by exposure the cells to the (center dot)NO donor, above 200 nmol DOPAC/10(6) cells, the cell death was not only enhanced but encompassed a distinct mechanism. Loading the cells with dopamine mimicked the effects of DOPAC.