Oestrogen receptors

 

 Dynamics and Vagaries of oestrogen signalling in males and females.!!!  ERs (Oestrogen receptors) have five domains with distinct functions .

 

Q.1: Which site of oestrogen receptor is most dynamic and not just lazy like Dr. Pal?? The N-terminal of the A/B domains of ERs consist of activation function 1 (AF1), which contributes to the transcriptional activity of ERs and is an essential domain for interaction with co-regulators.

Q. 2: How many of us believe that Oestrogens exerts its action via nuclear receptors(NRs-Nuclear Receptors)  unlike insulin?? . Ans:              Insulin receptors act on cytoplasmic mm but estrogen receptors (ERs) which belong to the steroid hormone superfamily of nuclear receptors (NRs) are situated at nuclear mm.

 Q,  3 :What  are the Other types of steroid receptors  exhibiting  action as of nuclear receptors?  Ans: Other types of steroid receptors exerting their actions on nuclear receptors among the NRs(nuclear receptors)  include the estrogen-related receptors (EER), progesterone receptors (PR), androgen receptors (AR), glucocorticoid, and mineral corticoid receptors.

 

Q.4:-Estrogens, a class of steroid hormones, regulate the growth, development, and physiology of the human reproductive system. Estrogens also involve in the neuroendocrine, skeletal, adipogenesis, and cardiovascular systems. Estrogen signaling pathways are selectively stimulated or inhibited depending on a balance between the activities of estrogen receptor (ER) α or ERβ in target organs. ERs belong to the steroid hormone superfamily of nuclear receptors, which act as transcription factors after binding to estrogen. The gene expression regulation by ERs is to modulate biological activities, such as reproductive organ development, bone modeling, cardiovascular system functioning, metabolism, and behavior in both females and males. Understanding of the general physiological roles of ERs has been gained when estrogen levels were ablated by ovariectomy and then replenished by treatment with exogenous estrogen. This technique is not sufficient to fully determine the exact function of estrogen signaling in general processes in living tissues. However, a transgenic mouse model has been useful to study gene-specific functions. ERα and ERβ have different biological functions, and knockout and transgenic animal models have distinct phenotypes. Analysis of ERα and ERβ function using knockout mouse models has identified the roles of estrogen signaling in general physiologic processes. Although transgenic mouse models do not always produce consistent results, they are the useful for studying the functions of these genes under specific pathological conditions.

Keywords: Estrogen, estrogen receptors, knockout mice

Estrogen receptors (ERs) belong to the steroid hormone superfamily of nuclear receptors (NRs) .Other types of steroid receptors among the NRs include the estrogen-related receptors (EER), progesterone receptors (PR), androgen receptors (AR), glucocorticoid, and Estrogen also affects the neuroendocrine, skeletal, adipogenic, and cardiovascular systems .

Q.5 : How many oest receptors are there?? The biological functions of estrogen are mediated by binding to the ERs: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ).

 

Q. 6 : How estrogen signalling is governed ?  Who finally dictate the mode of action in a particular cell ?

Ans: Estrogen signaling is selectively stimulated or inhibited depending upon a balance between ERα and ERβ activities in target organs. ERα has been cloned from human breast cancer MCF-7 cells in 1986 and ERβ was cloned from rat prostate in 1996

Q. 7: Where are gens for oestrogen domiciled  in which chromose ?? ERα and ERβ are encoded by distinct genes located on different chromosomes. The human ERα gene is located on chromosome 6 while the ERβ gene is on chromosome 14 .

Q.8: How many amino acides are there in ERα and in Erβ ??Ans:. The full-length human ERα protein has 595 amino acids and a molecular size of 66 kDa while the full-length human ERβ protein has 530 amino acids and a molecular size of 54 kDa. Similar to other NRs(nuclear receptors) , ERs have five domains with distinct functions . The N-terminal of the A/B domains of ERs consist of activation function 1 (AF1), which contributes to the transcriptional activity of ERs and is an essential domain for interaction with co-regulators. AF1 is the least conserved region with only 30% identity between ERα and ERβ. Functional studies have shown that ERβ has low levels of AF1 activity. The A/B domains also contain amino acids that are targets of post-transcriptional modifications including splicing to stimulate AF1 activity .

The C domain encodes a centrally located DNA binding domain (DBD) essential for sequence-specific binging of ERs to DNA and regulating the expression of target genes .

The D domain, a hinge region, includes amino acid sequences that stimulate nuclear localization signaling and facilitate post-translational modification of ERs, resulting in the activation of ER signaling in cells. Finally, the E/F domain, located in the C-terminal region, contains a ligand-binding domain (LBD) that serves as an interaction site with co-regulators and ligand-dependent activation function 2 (AF2).mineral corticoid receptors.