Estrogen is a family of steroid hormones that regulates multiple neural functions in the human body. They are grouped into three main types: estrone (E1), estriol (E2) and 17b-estradiol (E2). These hormones are produced by the endocrine system of the female body, including the ovary and the adrenal glands. These compounds are important in the development of many sexual and non-sexual characteristics.
Estrogens are involved in the onset of menstruation, the development of breasts, and the maturation of the skeleton. They are also associated with memory and learning. In addition, they affect many social behaviors.
Estrogens are synthesized in the ovary and adrenal glands and are present at low levels in the blood of the non-pregnant human. During pregnancy, these hormones are primarily secreted by the corpora lutea and the granulosa cells of the ovarian follicles. They have been found to have a significant impact on other organs in the reproductive system and on the brain.
Estrogen signaling is highly dependent on epigenetic mechanisms. In order to ensure accurate integration of estrogen signaling, co-regulators play an essential role. They carry out transcriptional activation and repression and generate available ER binding sites.
Estrogen receptors are involved in the induction of direct and indirect genomic signaling. They are located in the nucleus and cytoplasm. These receptors can bind directly to DNA sequences or indirectly to ligands. When ligands bind to the receptors, they induce structural changes in the receptor. The receptors can then activate intracellular cascades. The receptors are composed of a conserved C region corresponding to the DNA-binding domain and a distal box. The distal box is responsible for receptor dimerisation. The DNA-binding domain is important for ER recognition. It binds to specific sequences in chromatin.
The binding of ERs to other transcription factors leads to the recruitment of a multiprotein complex to transcriptional start sites. These promote phosphorylation and subsequently the expression of target genes. Moreover, ERs interact with a number of coregulators, which exhibit chromatin-modifying activities. Some of these coregulators, including AF-2, activate protein-kinase cascades. Some of these coregulators, such as fulvestrant and tamoxifen, have been shown to repress ERa target genes.
These proteins, known as epigenetic co-regulators, play an important role in the regulation of ER-driven responses. They are engaged in post-induction chromatin modulations and pre-induction chromatin modulations. Some of them have been linked to a variety of diseases.
Several of these proteins have been investigated in relation to breast cancer. One such protein, the estrogen receptor-alpha, is implicated in the development of mammary tumors. Another important protein, GPER1, is membrane-bound and is a key element in the rapid non-genomic actions of estrogens.
Other epigenetic co-regulators are involved in the maintenance of tissue-specificity of the estrogen-driven response. Some of them, such as microRNAs, influence the expression of ERs. Others, such as NF-kappa B and p53, are essential for maintaining the integrity of the ER-driven response.
The role of these factors in the endocrine system is not yet well-understood. They may provide a protective or inhibitory effect on the endocrine system, depending on the tissue type.