No abstract

Nuclear receptors (NRs) regulate transcription in a ligand-dependent way through two types of coactivator complexes: the p160/CBP histone acetyl transferase (HAT) complex and the DRIP/TRAP/SMCC complex without HAT activity. Here we identified a large human (h) coactivator complex necessary for the estrogen receptor alpha (ERalpha) transactivation. This complex contains the GCN5 HAT, the c-Myc interacting protein TRRAP/PAF400, TAF(II)30, and other subunits. Similarly to known TFTC (TBP-free TAF(II)-containing)-type HAT complexes (hTFTC, hPCAF, and hSTAGA), TRRP directly interacted with liganded ER alpha, or other NRs. ER alpha transactivation was enhanced by the purified complex in vitro. Antisense TRRAP RNA inhibited estrogen-dependent cell growth of breast cancer cells. Thus, the isolated TFTC-type HAT complex acts as a third class of coactivator complex for NR function.

Alzheimer’s disease(AD) is associated with a variety of pathophysiological features, including amyloid plaques, inflammation, immunological changes, cell death and regeneration processes, altered neurotransmission, and age-related changes. Retinoic acid receptors (RARs) and retinoids are relevant to all of these. Here we review the pathology, pharmacology, and biochemistry of AD in relation to RARs and retinoids, and we suggest that retinoids are candidate drugs for treatment of AD.

No abstract

A number of alkylphenolic compounds are used in a variety of commercial products and have been shown in in vitro studies to be weakly estrogenic, but few in vivo data are available addressing this issue in mammals. Human ex-posure to alkylphenols may occur not only from these environmental contaminants but also through contact with manufactured and metabolic breakdown products. The reproductive function of rats treated subcutaneously with nonylphenol (NP, 500 mg/kg/day) or 17Q3-estradiol (E2, 2 mg/kg/day) as a positive control, from postnatal days 1 to 5 was examined after puberty. In addition, masculine sexual behavior, sperm motion, plasma testosterone concentration and histopathological changes in the reproductive organs of the rats were examined. Furthermore, male rats were subjected to an open field test and wheel cage test to evaluate locomotor activity, and the estrous cycle was examined in female rats. All male and female rats exposed neonatally to NP or E2 showed macroscopic and/or microscopic altera-tions of the gonads. Females treated with NP or E2 showed an altered estrous cycle and abnormal reproductive function, while males treated with NP or E2 showed normal reproduc-tion. In males exposed neonatally to NP or E2, no abnorm-alities were observed in locomotor activity, sperm motion or plasma testosterone concentration. The results of this study indicate that early neonatal exposure to NP causes dysfunc-tion of postpubertal reproductive function in female rats, as well as disrupted development of gonads in male and female rats. More detailed studies are warranted to assess the possible risks to human and wildlife reproduction from exposure to NP and other environmental chemicals with estrogenic activity.