Estrogen receptor alpha (Esr1) regulates aromatase (Cyp19a1) expression in the mouse brain.

OBJECTIVES: Local estrogen production in the brain regulates critical functions including neuronal development, gonadotropin secretion and sexual behavior. In the mouse brain, a 36 kb distal promoter (l.f) regulates the Cyp19a1 gene that encodes aromatase, the key enzyme for estrogen biosynthesis. In vitro, promoter l.f interacts with estrogen receptor alpha (Esr1) to mediate Cyp19a1 mRNA expression and enzyme activity in mouse hypothalamic neuronal cell lines. The in vivo mechanisms that control mammalian brain aromatase expression during fetal and adult development, however, are not thoroughly understood. Our aim was to elucidate the basis of the in vivo connection between Esr1 and Cyp19a1. METHODS: Pregnant mice were sacrificed at gestational days 9, 11, 13, 15, 16, 19, 21 and the brain tissues of the fetuses were harvested along with five newborns at the age of postnatal day 2. Esr1KO (female) were also sacrificed and their hypothalamus were excised out. Then both fetuses and adults RNA were isolated, reverse transcribed and amplified employing primers specific for Esr1 and Cyp19a1 with Real time PCR. RESULTS: In the fetal mouse brain, Cyp19a1 mRNA levels are inversely correlated with estrogen receptor alpha (Esr1) mRNA levels in a temporal manner. Moreover, Cyp19a1 mRNA levels increased in the hypothalamus of estrogen receptor-alpha knockout female mice (Esr1KO). CONCLUSION: Taken together, our findings might indicate that Esr1 has crucial roles in the in vivo regulation of aromatase expression in the brain during fetal and adult life.

Paraoxonase levels in women with polycystic ovary syndrome.

OBJECTIVE: To determine paraoxonase (PON1) levels and whether paraoxonase activity is associated with an increased propensity for the development of cardiovascular disease in women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Thirty-one subjects with PCOS and 33 healthy controls were evaluated in this controlled clinical study. Lipid subfractions, fasting glucose, insulin and other hormone (gonadotropin, androgen) and PON1 levels were measured. Homeostasis model assessment (HOMA-R) was used to estimate insulin resistance. Statistical analysis was made with Student's t test and Pearson correlation analysis. RESULTS: The women with PCOS had significantly lower serum high-density lipoprotein (HDL), apolipoprotein A1, basal PON1, arylesterase and salt-stimulated PON1 (SSP) levels than did the controls. Also, fasting insulin levels and HOMA-R were significantly higher in women with PCOS as compared with healthy subjects. Basal PON1 was positively associated with apolipoprotein A1, arylesterase and SSP but inversely correlated with HOMA-R. HDL was negatively associated with fasting insulin and HOMA-R. CONCLUSION: Decreased PON1 activity might contribute to an increased propensity for the development of cardiovascular disease in women with PCOS in addition to known risk factors, such as insulin resistance, hypertension, dyslipidemia and increased oxidative stress.

Single dose nasal 17beta-estradiol administration reduces sympathovagal balance to the heart in postmenopausal women.

AIM: Long-term estrogen replacement therapy has favorable results on autonomic cardiovascular functions in postmenopausal women. Although acute estrogen administration has beneficial modulations on autonomic tone in animal studies, there are still controversies about the effects of acute estrogen on autonomic modulation to the heart in humans. The aim of this double-blind study was to investigate the acute effects of intranasal 17beta-estradiol administration on autonomic control of heart rate. METHODS: Nineteen postmenopausal women with typical hormone profiles were crossover randomized to 300 micro g nasal 17beta-estradiol (Aerodiol, Servier, Chambray-les-Tours, France) or an identical placebo at least 5 days apart. Both time domain and frequency domain heart rate variability (HRV) parameters were obtained during controlled respiration (CR) and handgrip exercise (HGE), before and 45 min after 17beta-estradiol or placebo administration. RESULTS: Baseline HRV parameters were similar for each occasion. Time domain indices obtained after 17beta-estradiol administration were not significantly different from results obtained with the placebo. In frequency domain parameters, 17beta-estradiol administration resulted in a reduced low frequency to high frequency ratio (LF/HF ratio) when compared with the placebo during CR (0.72 +/- 0.09 vs 1.00 +/- 0.15, P < 0.05) but not during HGE (3.03 +/- 0.37 vs 2.86 +/- 0.30, P > 0.05). CONCLUSION: A single intranasal 17beta-estradiol administration acutely reduced sympathovagal balance to the heart during the course of parasympathetic maneuver in healthy postmenopausal women.