Endogenous Estrogen Influences Predator Odor-Induced Impairment of Cognitive and Social Behaviors in Aromatase Gene Deficiency Mice

Epidemiological studies have suggested that traumatic stress increases vulnerability to various mental disorders, such as dementia and psychiatric disorders. While women are more vulnerable than men to depression and anxiety, it is unclear whether endogenous estrogens are responsible for the underlying sex-specific mechanisms. In this study, the aromatase gene heterozygous (Ar+/-) mice were used as an endogenous estrogen deficiency model and age- and sex-matched wild type mice (WT) as controls to study the predator odor 2,3,5-trimethyl-3-thiazoline- (TMT-) induced short- and long-term cognitive and social behavior impairments. In addition, the changes in brain regional neurotransmitters and their associations with TMT-induced changes in behaviors were further investigated in these animals. Our results showed TMT induced immediate fear response in both Ar+/- and WT mice regardless of sexes. TMT induced an acute impairment of novel object recognition memory and long-term social behavior impairment in WT mice, particularly in females, while Ar+/- mice showed impaired novel object recognition in both sexes and TMT-elevated social behaviors, particularly in males. TMT failed to induce changes in the prepulse inhibition (PPI) test in both groups. TMT resulted in a slight increase of DOPAC/DA ratio in the cortex and a significant elevation of this ratio in the striatum of WT mice. In addition, the ratio of HIAA/5-HT was significantly elevated in the cortex of TMT-treated WT mice, which was not found in TMT-treated Ar+/- mice. Taken together, our results indicate that TMT exposure can cause cognitive and social behavior impairments as well as change catecholamine metabolism in WT mice, and endogenous estrogen deficiency might desensitize the behavioral and neurochemical responses to TMT in Ar+/- mice.

Impact of estrogen replacement on growth, skeletal maturation, bone density and body composition in a girl with novel aromatase gene mutation

Aromatase deficiency is a rare autosomal recessive disorder characterized by impaired androgen to estrogen conversion. We report a 13.5-year-old girl initially misdiagnosed as simple virilising 21 hydroxylase deficiency who presented with delayed puberty. Work-up showed aromatase deficiency due to novel mutation in the aromatase gene. Estradiol replacement was associated with increased growth, skeletal maturation, bone density and adiposity. Early estrogen treatment in our case may have prevented metabolic complications and ovarian cysts.

Expression of cytochrome P450 aromatase isoforms in female Alburnus tarichi (Guldenstaedtii, 1814)

In this study, we aimed to clone brain-derived Cyp19b and ovary-derived Cyp19a the P450 aromatase gene isoforms and to indicate the expression levels of these genes in the hypothalamus and ovary tissues from reproductively arrested ovarian development (RA) and non-arrested ovarian development (RN) Alburnus tarichi from Lake Van, Turkey. The expression levels of Cyp19b and Cyp19a genes were predominant in the hypothalamus and ovary, respectively. The level of Cyp19b mRNA was significantly lower in the hypothalamus and ovary from RA fish than in the hypothalamus and ovary from RN fish (P<0.05). The expression level of Cyp19a was significantly lower in the ovary of RA fish (P<0.05) than RN fish while no difference was found in the hypothalamus of both RA and RN fish (P<0.05). According to these findings, we suggest that the RA fish represent a segment of the population and these fish may be more sensitive to endocrine disruption compound/s than others.

Calcitriol Revises Aromatase Gene Expression in Ehrlich Solid Tumor Bearing Mice Exposed to Low Dose Gamma Radiation

Background: Dysregulation of aromatase expression had been monitored in many types of cancer. Our study aimed to evaluate the possible role of calcitriol (Cal; Vit D3-OH) or/and low dose of gamma radiation in regulation of aromatase gene expression and the regression of tumor proliferation in murine model (EST; Ehrlich solid tumor bearing mice). Methods: Mice with ≈1 cm3 EST were received (i.p. injection) day after day repeated doses of Calcitriol (Cal) (0.05µg/mouse) for 14day or/and exposed to 0.5 Gy gamma radiation (low dose) delivered as one shot at dose rate 0.48 Gy/min. Results: Our results demonstrated that, mRNA expression of aromatase, levels of cyclooxygenase (COX2) and prostaglandin (PGE2) in addition to volume of the tumor are significantly decreased while caspase 3 level is significantly increased in EST mice treated with Cal or/and exposed to 0.5 Gy gamma ray compared to untreated EST bearing mice. However, the most pronounced improvements in all of the measured parameters were obviously indicated in EST mice group treated with Cal and exposed to gamma radiation. This was accomplished by suppression of inflammatory markers which cause down regulation in aromatase mRNA expression as well as augmenting apoptosis by inducing Caspase3 concentration. Conclusion: It could be concluded that the exposure to low dose gamma radiation potentiate the action of Calcitriol against tumor growth in the subjected murine model which represent a prospective policy for the management of solid tumor and decreasing the possibilities of tumor drug resistance.

The Association between Aromatase Gene Polymorphism Cyp19 Val 80 and Endometriosis Risk

Background: Endometriosis implant has been known to express aromatase enzyme, Cytochrome p450 that catalyzes androgen into estrogen. It causes local estrogen production, leading to increased estrogen level, and subsequently triggers endometriosis lesion. CYP19 gene resided at chromosome 15q21.1 is the biggest component of aromatase coding cytochrome p450 enzyme. Objective: To identify relationship between aromatase gene polymorphism CYP19 Val 80 and the risk of endometriosis. Methods: This is an observational case-control study using frozen DNA sample from women with endometriosis and/ or adenomyosis who had undergone laparotomy/ laparoscopy at Obstetrics and Gynecology Department Dr. Mohammad Hoesin General Hospital Palembang January-November 2013. Samples were amplified and cut by PCR-FRLP using Rsa1 restriction enzyme. Results were divided into A/A genotype (homozygote mutant), G/A (heterozygote mutant), and G/G (homozygote wild type). Data were analyzed by SPSS 21.0 version. Results: PCR-RFLP results for A/A genotype were 20 (21.3%) in endometriosis group and 8 (8.5%) in control group. G/A genotype were 18 (19.1%) in endometriosis group and 22 (23.4%) in control group. G/G genotype were 9 (9.6%) and 17 (18.1%) in endometriosis group and control group, respectively. There was significant increase risk of endometriosis in women carrying genotype A/A to those with genotype G/G with OR 4.722 (p<0.05). Conclusion: Polymorphism on aromatase gene CYP19 Val 80 A/A increases risk of endometriosis.

The Association between Aromatase Gene Polymorphism Cyp19 Val 80 and Endometriosis Risk

A B S T R A C TIntroduction: Endometriosis implant has been known to express aromataseenzyme, Cytochrome p450 that catalyzes androgen into estrogen. It causes localestrogen production, leading to increased estrogen level, and subsequently triggersendometriosis lesion. CYP19 gene resided at chromosome 15q21.1 is the biggestcomponent of aromatase coding cytochrome p450 enzyme. Objective: To identifyrelationship between aromatase gene polymorphism CYP19 Val 80 and the risk ofendometriosis. Methods: This is an observational case-control study using frozenDNA sample from women with endometriosis and/ or adenomyosis who hadundergone laparotomy/ laparoscopy at Obstetrics and Gynecology Department Dr.Mohammad Hoesin General Hospital Palembang January-November 2013. Sampleswere amplified and cut by PCR-FRLP using Rsa1 restriction enzyme. Results weredivided into A/A genotype (homozygote mutant), G/A (heterozygote mutant), andG/G (homozygote wild type). Data were analyzed by SPSS 21.0 version. Results:PCR-RFLP results for A/A genotype were 20 (21.3%) in endometriosis group and 8(8.5%) in control group. G/A genotype were 18 (19.1%) in endometriosis group and22 (23.4%) in control group. G/G genotype were 9 (9.6%) and 17 (18.1%) inendometriosis group and control group, respectively. There was significant increaserisk of endometriosis in women carrying genotype A/A to those with genotype G/Gwith OR 4.722 (p<0.05). Conclusion: Polymorphism on aromatase gene CYP19 Val80 A/A increases risk of endometriosis.