Regulation of cortical functions by estradiol

The sex hormone 17β-estradiol (E2) is primarily synthesized in maturing ovarian follicles. Cyclic changes in serum E2 levels across the menstrual cycle exert profound effects on reproductive tissues in women. E2 also plays an important role in the maintenance of normal limbic and cortical functions. Around menopause, when E2 levels decline the incidence of cognitive and mood disorders increases, which can be prevented with hormone replacement therapy. A major research interest of the Laboratory has been in the molecular mechanisms whereby E2 preserves good mood, capability of learning and processing memory via interactions with cortical and limbic structures. The classic actions of E2 are mediated by two estrogen receptor isoforms, ERα and ERβ. They are ligand-dependent transcription factors which regulate gene expression in the presence of E2. Prefrontal cortex (PFC) and the hippocampus are known targets of steroid hormone signaling.

 

The Laboratory has studied the genomic responses of the prefrontal cortex and the hippocampus to E2 replacement and treatments with ERα and ERβ selective agonists. Estrogen receptor agonist-regulated genes were identified by microarray technology and selected changes were confirmed by quantitative real-time PCR. Several E2-regulated transcripts were also localized with high-resolution in situ hybridization and immunocytochemical techniques.

 

·         In the PFC, genomic alterations in response to E2 were partly related to dopaminergic neurotransmission, immune surveillance, and transport processes.

 

·         In the hippocampal formation, ovariectomy and subsequent treatment with estrogen receptor agonists powerfully tuned the innate immune system of middle-aged female rats. Analogous changes were observed in the hippocampus of post-menopausal women. The results shed light on the molecular mechanisms whereby estrogen replacement therapy preserves cortical and limbic functions.

 

 

B. Balla, M. Sárvári, J. P. Kósa, B. Kocsis-Deák, B. Tobiás, K. Árvai, I. Takács, J. Podani, Z. Liposits, and P. Lakatos, “Long-term selective estrogen receptor-beta agonist treatment modulates gene expression in bone and bone marrow of ovariectomized rats,” JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, vol. 188, pp. 185–194, 2019.

 

M. Sarvari, I. Kallo, E. Hrabovszky, N. Solymosi, and Z. Liposits, “Ovariectomy Alters Gene Expression of the Hippocampal Formation in Middle-Aged Rats.,” ENDOCRINOLOGY, vol. 158, no. 1, pp. 69–83, 2017.

 

M. Sarvari, I. Kallo, E. Hrabovszky, N. Solymosi, A. Rodolosse, and Z. Liposits, “Long-Term Estrogen Receptor Beta Agonist Treatment Modifies the Hippocampal Transcriptome in Middle-Aged Ovariectomized Rats.,” FRONTIERS IN CELLULAR NEUROSCIENCE, vol. 10, p. 149, 2016.

 

M. Sarvari, I. Kallo, E. Hrabovszky, N. Solymosi, A. Rodolosse, C. Vastagh, H. Auer, and Z. Liposits, “Hippocampal Gene Expression Is Highly Responsive to Estradiol Replacement in Middle-Aged Female Rats.,” ENDOCRINOLOGY, vol. 156, no. 7, pp. 2632–2645, 2015.

 

M. Sárvári, L. Deli, P. Kocsis, L. Márk, G. Maász, E. Hrabovszky, I. Kalló, D. Gajári, C. Vastagh, B. Sümegi, K. Tihanyi, and Z. Liposits, “Estradiol and isotype-selective estrogen receptor agonists modulate the mesocortical dopaminergic system in gonadectomized female rats,” BRAIN RESEARCH, vol. 1583, no. 1, pp. 1–11, 2014.

 

M. Sarvari, P. Kocsis, L. Deli, D. Gajari, S. David, Z. Pozsgay, N. Hegedus, K. Tihanyi, and Z. Liposits, “Ghrelin Modulates the fMRI BOLD Response of Homeostatic and Hedonic Brain Centers Regulating Energy Balance in the Rat.,” PLOS ONE, vol. 9, no. 5, 2014.

 

M. Sarvari, I. Kallo, E. Hrabovszky, N. Solymosi, and Z. Liposits, “Ovariectomy and subsequent treatment with estrogen receptor agonists tune the innate immune system of the hippocampus in middle-aged female rats.,” PLOS ONE, vol. 9, no. 2, p. e88540, 2014.

 

M. Sarvari, E. Hrabovszky, I. Kallo, N. Solymosi, I. Liko, N. Berchtold, C. Cotman, and Z. Liposits, “Menopause leads to elevated expression of macrophage-associated genes in the aging frontal cortex: rat and human studies identify strikingly similar changes.,” JOURNAL OF NEUROINFLAMMATION, vol. 9, no. 1, p. 264, 2012.

 

M. Sarvari, E. Hrabovszky, I. Kallo, N. Solymosi, K. Toth, I. Liko, J. Szeles, S. Maho, B. Molnar, and Z. Liposits, “Estrogens regulate neuroinflammatory genes via estrogen receptors alpha and beta in the frontal cortex of middle-aged female rats,” JOURNAL OF NEUROINFLAMMATION, vol. 8, no. 1, 2011.

 

 

M. Sarvari, I. Kallo, E. Hrabovszky, N. Solymosi, K. Toth, I. Liko, B. Molnar, K. Tihanyi, and Z. Liposits, “Estradiol Replacement Alters Expression of Genes Related to Neurotransmission and Immune Surveillance in the Frontal Cortex of Middle-Aged, Ovariectomized Rats,” ENDOCRINOLOGY, vol. 151, no. 8, pp. 3847–3862, 2010.

 

 

 

 

 

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