Neuropeptide Y activates urocortin 1 neurons in the nonpreganglionic Edinger-Westphal nucleus

Item does not contain fulltextCentral regulatory pathways promoting stress adaptation utilize various neurotransmitters/neuropeptides, such as urocortin 1 (Ucn1) and neuropeptide Y (NPY). Ucn1 is abundantly expressed in the nonpreganglionic Edinger-Westphal nucleus (npEW), where it is codistributed with NPY-immunoreactive (ir) terminals. A special role for both neuropeptides has been postulated in stress adaptation. Using double-labeling immunohistochemistry, we observed close appositions between NPY-ir terminals and neurons immunoreactive for Ucn1 in the rat, as well as in the human npEW. Therefore, we hypothesized that NPY might control the activity of Ucn1-positive neurons in the npEW. To test this hypothesis, NPY was injected into the lateral cerebral ventricle of rats, resulting in a strong activation of npEW Ucn1 neurons as revealed by Fos immunohistochemistry. Ucn1 mRNA was also upregulated in the npEW 2 hours after the injection of NPY. In a search for the type of NPY receptor that mediates this NPY-induced recruitment of npEW-Ucn1 cells, we found that the great majority of Ucn1 cells exhibited NPY Y5 receptor immunoreactivity, and only a few of the Ucn1 cells coexpressed the Y1 receptor. We concluded that NPY, via NPY Y5 and to a lesser extent via the Y1 receptors, exerts a stimulatory action on Ucn1 cells in the npEW. Further studies are currently in progress to elucidate the significance of this NPY-Ucn1 interaction in the npEW

Suppression of Extravillous Trophoblast Vascular Endothelial Growth Factor Expression and Uterine Spiral Artery Invasion by Estrogen during Early Baboon Pregnancy

We have shown that advancing the increase in maternal serum estrogen levels from the second to the first third of baboon pregnancy suppressed extravillous cytotrophoblast (EVT) spiral artery invasion. Because vascular endothelial growth factor (VEGF) promotes EVT invasion, the present study determined whether EVT VEGF expression is altered by prematurely elevating estrogen in early pregnancy. Placental basal plate was obtained on d 60 of gestation (term is 184 d) from baboons treated daily on d 25–59 with estradiol (0.35 mg/d sc), which increased maternal peripheral serum estradiol levels 3-fold above normal. Overall percentage of uterine arteries (25 to more than 100 μm in diameter) invaded by EVT assessed by image analysis in untreated baboons (29.11 ± 5.78%) was decreased 4.5-fold (P < 0.001) by prematurely elevating estrogen (6.55 ± 1.83%). VEGF mRNA levels in EVT isolated by laser capture microdissection from the anchoring villi of untreated baboons (6.77 ± 2.20) were decreased approximately 5-fold (P < 0.05, ANOVA) by estradiol (1.37 ± 0.29). Uterine vein serum levels of the truncated soluble fms-like receptor, which controls VEGF bioavailability, in untreated baboons (403 ± 37 pg/ml) were increased 3-fold (P < 0.01) by estrogen treatment (1127 ± 197 pg/ml). Thus, placental EVT expression of VEGF mRNA was decreased and serum soluble truncated fms-like receptor levels increased in baboons in which EVT invasion of the uterine spiral arteries was suppressed by advancing the rise in estrogen from the second to the first third of pregnancy. We suggest that VEGF mediates the decline in EVT vessel invasion induced by estrogen in early primate pregnancy