Selective estrogen receptor modulator effects in the rat brain

Autor: Mary L. Thomas, Nina Koldzic-Zivanovic, Charlotte H. Clarke, René De Beun, Kathryn A. Cunningham, Wenxia Zhou, Karsten Wassermann, Paul Stanley Bury
Rok vydání: 2002
Předmět:
medicine.medical_specialty
Serotonin
Pyrrolidines
Endocrinology
Diabetes and Metabolism
Ovariectomy
Hypothalamus
Estrogen receptor
Gene Expression
Nerve Tissue Proteins
Rats
Sprague-Dawley
Cellular and Molecular Neuroscience
Estrogen-related receptor alpha
Endocrinology
Mesencephalon
Internal medicine
medicine
Animals
Estrogen Receptor beta
Raloxifene
RNA
Messenger
Estrogen receptor beta
Serotonin Plasma Membrane Transport Proteins
Membrane Glycoproteins
Estradiol
Endocrine and Autonomic Systems
Chemistry
Body Weight
Estrogen Antagonists
Estrogen Receptor alpha
Brain
Membrane Transport Proteins
Amygdala
Rats
Tamoxifen
Receptors
Estrogen
Selective estrogen receptor modulator
Raloxifene Hydrochloride
Receptors
Serotonin
Female
Carrier Proteins
Levormeloxifene
Estrogen receptor alpha
Receptors
Serotonin
5-HT1
hormones
hormone substitutes
and hormone antagonists
medicine.drug
Zdroj: Neuroendocrinology. 75(1)
ISSN: 0028-3835
Popis: The effects in the brain of selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene have not yet been fully elucidated. Based upon the hypothesis that serotonin (5-HT)-steroid hormone interactions are important in mood regulation, we have compared six SERMs (tamoxifen, raloxifene, levormeloxifene, NNC 45-0781, NNC 45-0320, NNC 45-1506) with 17β-estradiol (E2) in terms of their ability to regulate mRNA levels of estrogen receptor (ER)α, ERβ, 5-HT1A receptor, and 5-HT reuptake transporter (SERT) in the midbrain, amygdala, and hypothalamus of ovariectomized (OVX) rats. Female rats (n = 6/group, 8 groups total) were OVX and allowed to recover for 2 weeks. During the third post-OVX week, rats were injected subcutaneously with E2 (0.1 mg/kg) or one of the SERMs (5 mg/kg) once per day for 7 days. Twenty-four hours after the last injection, tissue was collected for the determination of mRNA levels by ribonuclease protection assay (RPA). E2 treatment significantly decreased mRNA levels for ERα, ERβ, and SERT in midbrain and ERα in hypothalamus. Tamoxifen increased ERβ mRNA levels in hypothalamus, while raloxifene increased ERβ mRNA levels in amygdala. NNC 45-0320 decreased ERα mRNA in hypothalamus and decreased ERβ mRNA in amygdala. These results suggest that while SERMs are not full estrogen receptor agonists in the brain, the agonist/antagonist profiles for individual SERMs may differ among brain areas. This raises the possibility of developing new SERMs for selective functions in specific brain areas.
Databáze: OpenAIRE
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