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The role of estrogen receptor type beta in the control of gene expression in the supraoptic nucleus of the hypothalamus

Grant number: 20/12881-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2021
Effective date (End): December 31, 2021
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:Andre de Souza Mecawi
Grantee:Victor Jardim Duque
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The control of the hydromineral balance is essential for human's health. Responses to imbalances of it are controlled by neuroendocrine systems able of responding to small variations in osmolality and extracellular fluid volume. The hypothalamic neurohypophyseal system, formed by magnocellular neurons in the supraoptic (SON) and paraventricular (PVN) nuclei, is essential for the control of this balance. The endings of the magnocellular neurons, which form the neurohypophysis, secrete vasopressin (AVP) and oxytocin (OT) in response to hyperosmolality. Literature data show that the induction of extracellular fluid hyperosmolality is able of profoundly altering gene expression in the SON and PVN of rats, remodeling the function of the hypothalamic neurohypophyseal system to increase the synthesis and secretion of AVP. This plastic response for adequate control of AVP synthesis and secretion is sexually dimorphic and appears to be controlled by estrogen levels in females. Estrogens are steroid hormones classically known for stimulating ovulation in females and preparing the reproductive system for embryo development. In addition to reproductive function, estrogens act on several tissues through nuclear receptors of type ± and ² (ER-± and ER-²) and the G protein-coupled receptor, GPER, all found in the central nervous system. Recent studies have shown that activation of the ER-² receptor increases the sensitivity of magnocellular neurons to hyperosmolality. In addition, it was observed that the activation of this receptor increases the secretion of AVP in response to dehydration. Therefore, it is possible that estrogen modulates the expression of regulatory genes related to the plasticity of magnocellular neurons through the activation of the ER-² receptor and these genes are able to act in the control of AVP synthesis and secretion. To test this hypothesis, this work aims to evaluate the role of estrogen and the ER-² receptor in the control of gene expression changes related to the neurohypophyseal system in response to acute osmotic stimulation in female rats. With this study, we expect to establish the relationship and importance of the genomic action of estrogen and its ER-² receptor for neuroplasticity involved in the control of AVP synthesis and secretion in response to changes in the hydromineral balance.

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