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Exposure to the estrogen receptor alpha (ERα) ligand diethylstilbesterol (DES) between neonatal days 2 to 12 induces penile adipogenesis and adult infertility in rats. The objective of this study was to investigate the in vivo interaction between DES-activated ERα and the proadipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARγ). Transcripts for PPARs α, β, and γ and γ1a splice variant were detected in Sprague-Dawley normal rat penis with PPARγ predominating. In addition, PPARγ1b and PPARγ2 were newly induced by DES. The PPARγ transcripts were significantly upregulated with DES and reduced by antiestrogen ICI 182, 780. At the cellular level, PPARγ protein was detected in urethral transitional epithelium and stromal, endothelial, neuronal, and smooth muscular cells. Treatment with DES activated ERα and induced adipocyte differentiation in corpus cavernosum penis. Those adipocytes exhibited strong nuclear PPARγ expression. These results suggest a biological overlap between PPARγ and ERα and highlight a mechanism for endocrine disruption. [ABSTRACT FROM AUTHOR]

Explanations for the chemosensory abilities of newborn mammals focus primarily on food (milk) acquisition and communication (e.g., maternal–infant bonding). However, the relative importance of the main and accessory (vomeronasal) olfactory systems is hypothesized to differ at birth between altricial and precocial mammals. Strepsirrhines (lemurs and lorises) possess main and accessory olfactory systems, and vary in life-history traits related to infant dependency and maturation. Accordingly, this study examines the size and maturational characteristics of vomeronasal (VNNE) and olfactory (OE) neuroepithelia in strepsirrhines. Serially sectioned heads of 18 infant cadavers were examined microscopically for neuroepithelial distribution. Measurements were taken on the length of the nasal fossa on one side that was occupied by VNNE and OE. The data were corrected for body size using the cranial length or body mass, and were then examined for correlation with several life-history variables, as well as activity pattern. In addition, immunohistochemistry was used to identify cells in the VNNE and OE that express olfactory marker protein (OMP), a marker of mature olfactory neurons. Relative OE extent was not significantly correlated with any of the life-history variables. Relative VNNE length was negatively correlated with relative gestation length and relative neonatal mass (P<0.05). However, when we corrected for phylogenetic relationships, we found no significant correlations between either of the neuroepithelial measurements and life-history variables. Immunohistochemical findings suggest that OE has more OMP-reactive cells than VNNE in all species. OMP-reactive cells appear to be less numerous in diurnal species compared to most nocturnal species. These results indicate that the VNNE may be relatively longer at birth in altricial species. However, it remains uncertain how phylogeny and/or ontogeny may explain these findings. Am. J. Primatol. 69:74–85, 2007. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

We have previously shown that human alpha-defensins can block the release of IL-1beta from LPS-activated human monocytes. The objective of this study is to use defensins as tools to determine the molecular mechanism by which IL-1beta is processed and secreted from human monocytes. LPS-activated (20 ng/ml, 2 h), 35S-methionine-labeled (1 h) human monocytes were treated with human alpha-defensin HD-5 in the presence or absence of ATP, staphylococcal alpha-toxin (SAT), or nigericin (Nig) for 3 h. Media and cell-associated fractions were harvested separately. IL-1beta was recovered from each by immunoprecipitation and caspase-1 was examined by western blot analysis. It was found that HD-5 blocked the release of mature IL-1beta from cells treated with ATP or Nig, while HD-5 did not inhibit ATP- or Nig-induced caspase-1 activation and externalization. However, SAT-induced caspase-1 activation was blocked by HD-5 and cytosolic mature IL-1beta was not detected in cells treated with SAT and HD-5. To our knowledge, HD-5 is the first known endogenous inhibitor of IL-1beta release. This study suggest that although both IL-1beta and caspase-1 are detected in the extracellular milieu after ATP stimulation, mature IL-1beta and its converting enzyme caspase-1 are secreted via different pathways. [ABSTRACT FROM AUTHOR]