Steroid Hormones, Hormone Secretion, and Steroid Receptors in Carcinogenesis
Velibor Krsmanović, James F. Whitfield in Malignant Cell Secretion, 2019
Extragenomic events preceding gene expression play an important role in signal transduction mechanism(s). Signal transduction involves a rapid cascade of events such as phosphorylation, methylations, and acetylations of preformed regulatory proteins.3,8,9,21 These modifications control the activities of regulatory proteins.8,9 There is a large family of genes whose products are transcriptional regulatory proteins.25 The steroid hormone receptors are a family of regulatory proteins whose ability to control gene activity (expression) depends on their activation by their steroid ligands. Steroid receptors are phosphoproteins.32-34,113 They are also substrates for cAMP-dependent protein kinase which promotes steroid receptor functions.100 There is a resemblance between function of the cAMP-dependent protein kinase and glucocorticoid receptor systems, both of which have kinase activity and play important roles in the mechanism of signal transduction.
Biology of the endometrium
Barry G. Wren in Progress in the Management of the Menopause, 2020
In addition to steroid hormones, their receptors play a key role in the regulation of cellular events in the endometrium. Estrogen and progesterone receptors are in tracellularly located ligand-inducible transcription factors that interact with specific hormone-response elements in target genes4,5. The three different domains of the receptor molecule possess specific functions (e.g. steroid and DNA-binding domains). A revolution in receptor studies was the realization that steroid hormone receptors are associated with non-steroid binding proteins that play a role in regulation of receptor function. Some of those proteins, such as heat shock protein 90, are speculated to stabilize the unactivated form of the steroid receptor in the absence of hormone6. The steroid-controlled regulatory genes can further regulate the expression of a multitude of genes either via transcription or post-transcriptional pathways. Some of the final protein products may remain intracellular; others are secreted and capable of mediating the steroid action to other cells. Figure 1 schematically represents a simplified model of signal transduction by steroid receptors. Despite many significant advances in the field of molecular biology, our understanding of how steroid receptors regulate gene transcription is still at an early stage.
Radiotracer Interactions with Sex Steroid Hormone Receptor Proteins (Receptor Mapping)
Lelio G. Colombetti in Principles of Radiopharmacology, 1979
The sex steroid hormone receptors are proteins located in the cytoplasm of the target tissue cells. To be called hormone receptors, these proteins must fulfill the following requirements:8They must display a high structural specificity that is in compliance with known structure-activity relationships.The number of binding sites must be limited (low capacity).The occurrence of receptors in various tissues should correlate with the observed response to the hormone.The receptor must have a high affinity for the hormone that is normally present in plasma in very low concentrations.The hormone-receptor interaction must be reversible, in order to terminate the stimulation.
From ligands to behavioral outcomes: understanding the role of mineralocorticoid receptors in brain function
Published in Stress, 2023
Huanqing Yang, Sowmya Narayan, Mathias V. Schmidt
Steroid hormone receptors are ligand-activated and switch from an inactive state to an active state by binding to their corresponding hormones (Torchia et al., 1998). Since MR LBD shares high homology with GR LBD, MR has two main endogenous ligands: aldosterone and cortisol in humans, or CORT in rodents (Baker et al., 2013). MR has a high affinity for cortisol (Kd = 0.5 nM), 10-fold higher than GR (Kd = 5 nM) (Meijer et al., 2018). The circulating concentration of cortisol in the blood is about 100–1000 times that of aldosterone (Syed & Qureshi, 2012). Even if only 5%-10% of cortisol is actively free, cortisol levels remain much higher than aldosterone in plasma (Cizza & Rother, 2012; Mifsud & Reul, 2018). Consequently, MR will be entirely occupied by cortisol except for when the circadian cycle of cortisol release is at its lowest point. Aldosterone has the same affinity for binding MR as cortisol, and since aldosterone dissociates from MR more slowly than cortisol, the aldosterone-MR complex is more stable and potent.
Low-dose ionizing radiation attenuates mast cell migration through suppression of monocyte chemoattractant protein-1 (MCP-1) expression by Nr4a2
Published in International Journal of Radiation Biology, 2019
Chin-Hee Song, Hae Mi Joo, So Hyun Han, Jeong-In Kim, Seon Young Nam, Ji Young Kim
The Nr4a orphan nuclear receptors are transcription factors belonging to the superfamily of steroid hormone receptors that are associated with a variety of cellular processes, including inflammation (Murphy et al. 2001; Pei et al. 2005), steroidogenesis (Maxwell and Muscat 2006), neuron development (Zetterstrom et al. 1997), and glucose metabolism (Pei et al. 2006). In contrast to other members of the steroid hormone receptor superfamily, the activity of these factors is regulated by cytokines, growth factors, and various other stimuli in a ligand-independent manner (Zhao and Bruemmer 2010). Among these factors, the expression of Nr4a2 (also known as Nurr1) is up-regulated following activation of primary mast cells and human mast cell lines (HMC-1 and LAD-2) (Zhang et al. 2010; Lundequist et al. 2011; Wang et al. 2014). Silencing of Nr4a2 gene expression has further been shown to reduce the production of cytokines in T cells (Doi et al. 2008).
Significance of DopEcR, a G-protein coupled dopamine/ecdysteroid receptor, in physiological and behavioral response to stressors
Published in Journal of Neurogenetics, 2020
Emily Petruccelli, Arianna Lark, James A. Mrkvicka, Toshihiro Kitamoto
Environmental stressors induce changes in, among others, endocrine states and stimulate the secretion of stress hormones such as cortisol. Steroid hormones were originally found to act through transcriptional regulation by nuclear steroid hormone receptors that function as steroid-dependent transcription factors, eliciting biological responses with a time lag of hours or even days (Beato, 1989; Evans, 1988). However, it has been known for a long time that steroids can also act via rapid mechanisms independent of transcriptional regulation, actions referred to as “nongenomic” responses to steroids. For example, it was reported as early as 1939 that estrogen rapidly exerts effects on peripheral blood vessels within 3–15 min (Reynolds & Foster, 1939). Selye (1942) also demonstrated that steroids, including cortisol, have an anesthetic effect in rats within minutes. Following these early reports, a number of studies have shown that steroid-mediated phenomena can occur very quickly, within seconds to minutes (Blackmore, Beebe, Danforth, & Alexander, 1990; Winter, Schneider, O’Sullivan, Harvey, & Geibel, 1999) and be observed even in cells lacking a functional nucleus, such as erythrocytes, platelets, or spermatozoa (Ivanova, Bernhardt, & Bernhardt, 2008; Moro et al., 2005; Shivaji & Jagannadham, 1992).
Related Knowledge Centers
- Estrogen
- Intracellular Receptor
- Nuclear Receptor
- Signal Transduction
- Steroid Hormone
- Cell Membrane
- Cell Nucleus
- Cytosol
- Receptor
- G Protein-Coupled Receptor