Megestrol acetate inhibits the expression of cytoplasmic aromatase through nuclear C/EBPβ in reperfusion injury-induced ischemic rat hippocampus.
Summary of "Megestrol acetate inhibits the expression of cytoplasmic aromatase through nuclear C/EBPβ in reperfusion injury-induced ischemic rat hippocampus."
Global ischemia after cardiac arrest, intraoperative hypoxia/hypotension, and hemorrhagic shock causes brain injury resulting in severe neurological and neurobehavioral deficits. Neurodegeneration can be prevented by local aromatase expression, and estrogen synthesis can be neuroprotective in ischemia/reperfusion. Therefore, aromatase, the enzyme that transforms androgens to estrogens, may be a potential target for the study of reperfusion injury after brain ischemia. We investigated the expression of aromatase and C/EBPβ using western blotting in rat hippocampus after transient global ischemia plus hypotension. Immunohistochemical analysis was performed for aromatase. After 10min of ischemia, aromatase and C/EBPβ expression in cytosolic extracts were observed after 10min and 24h of reperfusion. The expression of both proteins was similar in control and damaged tissues. Immunoblot analysis demonstrated that the highest aromatase expression appeared in damaged hippocampi after 1week and was gradually reduced after 2-10weeks. C/EBPβ expression increased at 1week in nuclear extracts of damaged hippocampi. The aromatase inhibitor megestrol acetate (20mg/kg/day) suppressed aromatase and nuclear C/EBPβ levels in ischemic hippocampi. Our findings indicate that ischemia as well as chronic neurodegenerative processes leads to an increase in cytoplasmic aromatase and nuclear C/EBPβ. Thus, it is possible to hypothesize an interaction between this enzyme gene and transcription factor.
Affiliation
Department of Pharmacology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey.
Journal Details
This article was published in the following journal.
Name: European journal of pharmacology
ISSN: 1879-0712
Pages: 217-25
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21114983
- DOI: http://dx.doi.org/10.1016/j.ejphar.2010.11.001
Medical and Biotech [MESH] Definitions
Megestrol Acetate
Megestrol acetate is a progestogen with actions and uses similar to those of the progestogens in general. It also has anti-androgenic properties. It is given by mouth in the palliative treatment or as an adjunct to other therapy in endometrial carcinoma and in breast cancer. Megestrol acetate has been approved to treat anorexia and cachexia. (From Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)
Megestrol
17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione. A progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer.
Aromatase Inhibitors
Compounds that inhibit AROMATASE in order to reduce production of estrogenic steroid hormones.
Gene Expression Regulation, Leukemic
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in leukemia.
Gene Expression Regulation, Plant
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in plants.
PubMed Articles
The distribution of IGF2 and IMP3 in osteosarcoma and its relationship with angiogenesis.
The aim of this study was to investigate the expression patterns of IGF2 and IMP3 in osteosarcoma as well as its relationship with angiogenesis in the tumor. IGF2 and IMP3 expression was detected by i...
Retinol inhibits aromatase activity and expression in vitro.
Aromatase converts androgens into estrogens and is thought to supply a local source of estrogen that facilitates the growth of hormone-responsive tumor cells. Inhibition of aromatase is therefore an i...
BACKGROUND AND OBJETIVE: Weight loss in patients with severe chronic obstructive pulmonary disease (COPD) is a prognostic bad factor. The objective of this study is to analyze the effectively of meges...
The vertebrae of prematurely aging mice as a skeletal model of involutional osteoporosis.
Yes-associated protein (YAP) is a transcriptional co-activator and functions as a nuclear downstream effector of the Hippo pathway. Differential expression of YAP and phosphorylated Yes-associated pro...
o,p'-Dichlorodiphenyltrichloroethane (o,p'-DDT) is a DDT isomer and xenoestrogen that can induce inflammation and cancer. However, the effect of o,p'-DDT on aromatase is unclear. Thus, we investigated...
Clinical Trials
To compare the effects of megestrol acetate and placebo on body weight, anorexia, cachexia, calorie intake, and nutritional parameters of patients with a confirmed diagnosis of AIDS. To de...
To determine the pharmacokinetics and safety of megestrol acetate after a single oral 300 mg dose of megestrol acetate concentrated suspension in healthy subjects, and subjects with varyin...
To compare the effects of megestrol acetate and placebo on body weight, anorexia, cachexia, calorie intake, and nutritional parameters of patients with a confirmed diagnosis of AIDS. To ch...
Study to Evaluate the Effect of Megestrol Acetate in Weight Loss in Dementia Patients
The purpose of this study is to demonstrate the efficacy of megestrol acetate in the gain of body weight in patients with primary or mixed Dementia with a weight loss.
To obtain data on the safety of administering megestrol acetate and dronabinol as single agents or in combination to patients with human immunodeficiency virus (HIV)-wasting syndrome. To o...
