Related Research Articles
An androgen is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes the embryological development of the primary male sex organs, and the development of male secondary sex characteristics at puberty. Androgens are synthesized in the testes, the ovaries, and the adrenal glands.
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids and sex steroids. Within those two classes are five types according to the receptors to which they bind: glucocorticoids and mineralocorticoids and androgens, estrogens, and progestogens. Vitamin D derivatives are a sixth closely related hormone system with homologous receptors. They have some of the characteristics of true steroids as receptor ligands.
A hormone receptor is a receptor molecule that binds to a specific chemical messenger. Hormone receptors are a wide family of proteins made up of receptors for thyroid and steroid hormones, retinoids and Vitamin D, and a variety of other receptors for various ligands, such as fatty acids and prostaglandins. Hormone receptors are of mainly two classes. Receptors for peptide hormones tend to be cell surface receptors built into the plasma membrane of cells and are thus referred to as trans membrane receptors. An example of this is Actrapid. Receptors for steroid hormones are usually found within the protoplasm and are referred to as intracellular or nuclear receptors, such as testosterone. Upon hormone binding, the receptor can initiate multiple signaling pathways, which ultimately leads to changes in the behavior of the target cells.
Steroid hormone receptors are found in the nucleus, cytosol, and also on the plasma membrane of target cells. They are generally intracellular receptors and initiate signal transduction for steroid hormones which lead to changes in gene expression over a time period of hours to days. The best studied steroid hormone receptors are members of the nuclear receptor subfamily 3 (NR3) that include receptors for estrogen and 3-ketosteroids. In addition to nuclear receptors, several G protein-coupled receptors and ion channels act as cell surface receptors for certain steroid hormones.
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors, which are members of the nuclear receptor family of intracellular receptors, and membrane estrogen receptors (mERs), which are mostly G protein-coupled receptors. This article refers to the former (ER).
Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it is called androgen-binding protein (ABP).
The androgen receptor (AR), also known as NR3C4, is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.
Intracrine refers to a hormone that acts inside a cell, regulating intracellular events. In simple terms it means that the cell stimulates itself by cellular production of a factor that acts within the cell. Steroid hormones act through intracellular receptors and, thus, may be considered to be intracrines. In contrast, peptide or protein hormones, in general, act as endocrines, autocrines, or paracrines by binding to their receptors present on the cell surface. Several peptide/protein hormones or their isoforms also act inside the cell through different mechanisms. These peptide/protein hormones, which have intracellular functions, are also called intracrines. The term 'intracrine' is thought to have been coined to represent peptide/protein hormones that also have intracellular actions. To better understand intracrine, we can compare it to paracrine, autocrine and endocrine. The autocrine system deals with the autocrine receptors of a cell allowing for the hormones to bind, which have been secreted from that same cell. The paracrine system is one where nearby cells get hormones from a cell, and change the functioning of those nearby cells. The endocrine system refers to when the hormones from a cell affect another cell that is very distant from the one that released the hormone.
Proline-, glutamic acid- and leucine-rich protein 1 (PELP1) also known as modulator of non-genomic activity of estrogen receptor (MNAR) and transcription factor HMX3 is a protein that in humans is encoded by the PELP1 gene. is a transcriptional corepressor for nuclear receptors such as glucocorticoid receptors and a coactivator for estrogen receptors.
Estrogen receptor alpha (ERα), also known as NR3A1, is one of two main types of estrogen receptor, a nuclear receptor that is activated by the sex hormone estrogen. In humans, ERα is encoded by the gene ESR1.
The vitamin D receptor (VDR also known as the calcitriol receptor) is a member of the nuclear receptor family of transcription factors. Calcitriol (the active form of vitamin D, 1,25-(OH)2vitamin D3) binds to VDR, which then forms a heterodimer with the retinoid-X receptor. The VDR heterodimer then enters the nucleus and binds to Vitamin D responsive elements (VDRE) in genomic DNA. VDR binding results in expression or transrepression of many specific gene products. VDR is also involved in microRNA-directed post transcriptional mechanisms. In humans, the vitamin D receptor is encoded by the VDR gene located on chromosome 12q13.11.
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These intracellular receptors work with other proteins to regulate the expression of specific genes thereby controlling the development, homeostasis, and metabolism of the organism.
The nuclear receptor coactivator 1 (NCOA1) is a transcriptional coregulatory protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA1 is recruited to DNA promotion sites by ligand-activated nuclear receptors. NCOA1, in turn, acylates histones, which makes downstream DNA more accessible to transcription. Hence, NCOA1 assists nuclear receptors in the upregulation of DNA expression.
G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans is encoded by the GPER gene. GPER binds to and is activated by the female sex hormone estradiol and is responsible for some of the rapid effects that estradiol has on cells.
Estrogen-related receptor beta (ERR-β), also known as ESRRB or NR3B2, is a nuclear receptor that in humans is encoded by the ESRRB gene.
3β-Androstanediol, also known as 5α-androstane-3β,17β-diol, and sometimes shortened in the literature to 3β-diol, is an endogenous steroid hormone and a metabolite of androgens like dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT).
Membrane androgen receptors (mARs) are a group of G protein-coupled receptors (GPCRs) which bind and are activated by testosterone and/or other androgens. Unlike the androgen receptor (AR), a nuclear receptor which mediates its effects via genomic mechanisms, mARs are cell surface receptors which rapidly alter cell signaling via modulation of intracellular signaling cascades. Known or proposed mARs include ZIP9 and GPRC6A.
Membrane glucocorticoid receptors (mGRs) are a group of receptors which bind and are activated by glucocorticoids such as cortisol and corticosterone, as well as certain exogenous glucocorticoids such as dexamethasone. Unlike the classical nuclear glucocorticoid receptor (GR), which mediates its effects via genomic mechanisms, mGRs are cell surface receptors which rapidly alter cell signaling via modulation of intracellular signaling cascades. The identities of the mGRs have yet to be fully elucidated, but are thought to include membrane-associated classical GRs as well as yet-to-be-characterized G protein-coupled receptors (GPCRs). Rapid effects of dexamethasone were found not be reversed by the GR antagonist mifepristone, indicating additional receptors besides just the classical GR.
Membrane mineralocorticoid receptors (mMRs) or membrane aldosterone receptors are a group of receptors which bind and are activated by mineralocorticoids such as aldosterone. Unlike the classical nuclear mineralocorticoid receptor (MR), which mediates its effects via genomic mechanisms, mMRs are cell surface receptors which rapidly alter cell signaling via modulation of intracellular signaling cascades. The identities of the mMRs have yet to be fully elucidated, but are thought to include membrane-associated classical MRs as well as yet-to-be-characterized G protein-coupled receptors (GPCRs). Rapid effects of aldosterone were found not be reversed by the MR antagonist spironolactone, indicating additional receptors besides just the classical MR. It has been estimated that as much as 50% of the rapid actions of aldosterone are mediated by mMRs that are not the classical MR, based on findings of insensitivity to classical mR antagonists.
Zinc transporter ZIP9, also known as Zrt- and Irt-like protein 9 (ZIP9) and solute carrier family 39 member 9, is a protein that in humans is encoded by the SLC39A9 gene. This protein is the 9th member out of 14 ZIP family proteins, which is a membrane androgen receptor (mAR) coupled to G proteins, and also classified as a zinc transporter protein. ZIP family proteins transport zinc metal from the extracellular environment into cells through cell membrane.
References
- ↑ Semicolons roughly denote structural groups, e.g. G-protein receptors from ion channels.
- 1 2 Levin ER (2014). "Translating extranuclear steroid receptor signaling to clinical medicine". Horm Cancer. 5 (3): 140–5. doi:10.1007/s12672-014-0179-9. PMC 4040225 . PMID 24752388.
- 1 2 Hammes SR, Levin ER (2011). "Minireview: Recent advances in extranuclear steroid receptor actions". Endocrinology. 152 (12): 4489–95. doi:10.1210/en.2011-1470. PMC 3858720 . PMID 22028449.
- 1 2 Sen A, Prizant H, Hammes SR (2011). "Understanding extranuclear (nongenomic) androgen signaling: what a frog oocyte can tell us about human biology". Steroids. 76 (9): 822–8. doi:10.1016/j.steroids.2011.02.016. PMC 4972037 . PMID 21354434.
- 1 2 Watson, C. S. (1999). "Signaling Themes Shared Between Peptide and Steroid Hormones at the Plasma Membrane". Science Signaling. 1999 (12): pe1. doi:10.1126/stke.1999.12.pe1. ISSN 1945-0877. PMC 1317563 . PMID 11865187.
- ↑ W.Norman, A.; Mizwicki, M. T.; Norman, D. G. (January 2004). "Steroid-hormone rapid actions, membrane receptors and a conformational ensemble model". Nature Reviews Drug Discovery. 3 (1): 27–41. doi:10.1038/nrd1283. PMID 14708019. S2CID 17487277.
- 1 2 3 4 5 6 7 Treviño, LS; Gorelick, DA (1 August 2021). "The Interface of Nuclear and Membrane Steroid Signaling". Endocrinology. 162 (8): bqab107. doi:10.1210/endocr/bqab107. PMC 8214340 . PMID 34038515.
- ↑ Gaucci E, Raimondo D, Grillo C, Cervoni L, Altieri F, Nittari G, et al. (November 2016). "Analysis of the interaction of calcitriol with the disulfide isomerase ERp57". Scientific Reports. 6: 37957. Bibcode:2016NatSR...637957G. doi:10.1038/srep37957. PMC 5126700 . PMID 27897272.
 | This article about a biochemical receptor is a stub. You can help Wikipedia by expanding it. |