Low sex steroids, high steroid receptors: Increasing the sensitivity of the nonreproductive brain

2007 ◽  
Vol 67 (1) ◽  
pp. 57-67 ◽  
Author(s):  
Virginie Canoine ◽  
Leonida Fusani ◽  
Barney Schlinger ◽  
Michaela Hau
Keyword(s):  
Sex Steroids ◽  
Steroid Receptors

scholarly journals Cloning of mouse 17β-hydroxysteroid dehydrogenase type 2, and analysing expression of the mRNAs for types 1, 2, 3, 4 and 5 in mouse embryos and adult tissues

1997 ◽  
Vol 325 (1) ◽  
pp. 199-205 ◽  
Author(s):  
Mika V. J. MUSTONEN ◽  
Matti H. POUTANEN ◽  
Veli V. ISOMAA ◽  
Pirkko T. VIHKO ◽  
Reijo K. VIHKO
Keyword(s):  
Sex Steroids ◽  
Steroid Receptors ◽  
Mouse Embryos ◽  
Key Factors ◽  
Reading Frame ◽  
Mouse Tissues ◽  
Low Activity ◽  
Oestradiol Production

17β-Hydroxysteroid dehydrogenases (17HSDs) are responsible for the conversion of low-activity sex steroids to more potent forms, and vice versa. 17HSD activity is essential for the biosynthesis of sex steroids in the gonads, and it is also one of the key factors regulating the availability of active ligands for sex-steroid receptors in various extragonadal tissues. In this study, we have characterized mouse 17HSD type 2 cDNA, and analysed the relative expression of 17HSD types 1, 2, 3, 4 and 5 mRNAs in mouse embryos and adult male and female tissues. The cDNA characterized has a open reading frame of 1146 bp, and encodes a protein of 381 amino acids with a predicted molecular mass of 41837 kDa. Northern-blot analysis of adult mouse tissues revealed that, of the different 17HSDs, the type 2 enzyme is most abundantly expressed. High expression of the enzyme, which oxidizes both testosterone and oestradiol, in several large organs of both sexes indicates that it is the isoform having the most substantial role in the metabolism of sex steroids. Interestingly, four of the five 17HSD enzymes were also detected by Northern blots of whole mouse embryos, and each of the enzymes showed a unique pattern of expression. The oestradiol-synthesizing type 1 enzyme predominates in early days of development embryonic day 7, but after that the oxidative type 2 enzyme becomes the predominant form of all 17HSDs. The data therefore suggest that there is transient oestradiol production in the early days of embryonic development, after which inactivation of sex steroids predominates in the fetus and placenta.

scholarly journals Extranuclear estrogen receptor's roles in physiology: lessons from mouse models

2014 ◽  
Vol 307 (2) ◽  
pp. E133-E140 ◽  
Author(s):  
Ellis R. Levin
Keyword(s):  
Mouse Models ◽  
Sex Steroids ◽  
Steroid Receptors ◽  
Sex Steroid ◽  
Normal Cells ◽  
Receptor Localization ◽  
Selective Agonists ◽  
And Function ◽  
Receptor Pool ◽  
Made In

Steroid receptors exist and function in multiple compartments of cells in most organs. Although the functions and nature of some of these receptors is being defined, important aspects of receptor localization and signaling to physiology and pathophysiology have been identified. In particular, extranuclear sex steroid receptors have been found in many normal cells and in epithelial tumors, where they enact signal transduction that impacts both nongenomic and genomic functions. Here, I focus on the progress made in understanding the roles of extranuclear estrogen receptors (ER) in physiology and pathophysiology. Extranuclear ER serve as a model to selectively intervene with novel receptor reagents to prevent or limit disease progression. Recent novel mouse models and membrane ER-selective agonists also provide a better understanding of receptor pool cross-talk that results in the overall integrative actions of sex steroids.

Action, localization and structure-function relationship of growth factors and their receptors in the prostate

1996 ◽  
Vol 5 (2) ◽  
pp. 73-105 ◽  
Author(s):  
S Chevalier ◽  
AG Aprikian ◽  
G Beauregard ◽  
I Defoy ◽  
LT Nguyen ◽  
...  
Keyword(s):  
Growth Factors ◽  
Cell Division ◽  
Sex Steroids ◽  
Steroid Receptors ◽  
Direct Action ◽  
Culture Conditions ◽  
Mitogenic Activity ◽  
Prostate Cell

Whereas the direct action of sex steroids, namely of androgens, on prostate cell division was questioned as early as in the 1970s, and remains so, the interest in prostatic growth factors (GFs) is rather recent but has expanded tremendously in the last five years. This lag period can be partly explained by the fact that, at the time, androgen receptors had just been discovered, and newly developed hormonal regimens or strategies to treat patients with prostate carcinoma (PCa) or epithelioma had generated great enthusiasm and hopes in the medical and scientific community. Another point to consider was the difficulty in maintaining prostate tissues in organ cultures and the relative novelty of culturing prostate epithelial cells in monolayers. Failures of sex steroids to elicit a direct positive response on prostate cell division in vitro, as seen in vivo, were interpreted as resulting from inappropriate models or culture conditions. However, the increasing number of reports confirming the lack of mitogenic activity of sex steroids in vitro, coupled with the powerful mitogenic activity of GFs displayed in other systems, the discovery of GF receptors (GF-Rs), and the elucidation of their signalling pathways showing sex steroid receptors as potential substrates of GF-activated protein kinases gradually led to an increased interest in the putative role of GFs in prostate physiopathology. Of utmost importance was the recognition that hormone refractiveness was responsible for PCa progression, and for the poor outcome of patients with advanced disease under endocrine therapies. This problem remains a major issue and it raises several key questions that need to be solved at the fundamental and clinical levels.

Sex steroid receptors in rheumatoid arthritis

2004 ◽  
Vol 106 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Masato ISHIZUKA ◽  
Masahito HATORI ◽  
Takashi SUZUKI ◽  
Yasuhiro MIKI ◽  
Andrew D. DARNEL ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Relative Abundance ◽  
Sex Steroids ◽  
Steroid Receptors ◽  
Inflammatory Cells ◽  
Sex Steroid ◽  
Rt Pcr ◽  
Sex Steroid Receptors ◽  
Synovial Tissues

Rheumatoid arthritis (RA) is a disease characterized primarily by chronic inflammatory synovitis and is well-known to be associated with significant sex differences in its prevalence and clinical features. Sex steroids have been proposed to be involved in the pathogenesis of RA, but details pertaining to the expression of sex steroid receptors in RA synovial tissue have yet to be fully characterized. In the present study, we examined oestrogen receptor (ER) α, ERβ, progesterone receptor (PR) and androgen receptor (AR) mRNA expression using real-time reverse transcriptase–PCR (RT-PCR) in eight female RA synovial tissues and six female synovial tissues without inflammation, and determined immunolocalization of ERα, ERβ, PR-A, PR-B and AR using immunohistochemistry in synovial tissues obtained from 22 RA patients. Real-time RT-PCR analysis demonstrated the expression of ER, PR and AR mRNAs in both RA and non-inflamed synovial tissues. Relative abundance of ER mRNAs was significantly higher in RA synovial tissue than non-inflamed synovial tissue (P<0.05). In addition, the relative ERα/ERβ mRNA expression ratio was significantly lower in RA than non-inflamed synovial tissue (RA, 2.34±1.60; and non-inflamed, 20.7±19.1; P<0.05). There were no significant differences in relative abundance of PR mRNA. Relative abundance of AR mRNA was significantly lower in RA (P<0.05). Immunoreactivity for ERα, ERβ, PR-B and AR was detected in the lining cells, inflammatory cells and fibroblasts in all the patients examined. The labelling indices for ERβ and PR-B were more abundant in both lining cells (ERβ, 54.2±12.2%; PR-B, 73.6±18.9%) and inflammatory cells (ERβ, 74.6±16.2%; PR-B, 75.9±16.1%) than in fibroblasts (ERβ, 36.5±15.6%; PR-B, 49.4±18.0%). Labelling indices for ERα and AR were significantly higher in lining cells (ERα, 14.4±8.6%; AR, 31.2±11.3%) and fibroblasts (ERα, 12.1±7.5%; AR, 20.1±9.6%) than those in inflammatory cells (ERα, 5.7±3.3%; AR, 9.2±4.4%). There were significant differences (P<0.05) in the labelling indices for ERα, ERβ and PR-B between men and women under 50 years of age in fibroblasts of RA synovial tissues. These results indicate that sex steroid receptors are present in RA and non-inflamed synovial tissues, including inflammatory cells in RA, and suggest that sex steroids may play important roles in the regulation of inflammation of RA synovial tissue.

Low sex steroids, high steroid receptors: Increasing the sensitivity of the nonreproductive brain

2006 ◽  
Vol 67 (1) ◽  
pp. 57-67 ◽  
Author(s):  
Virginie Canoine ◽  
Leonida Fusani ◽  
Barney Schlinger ◽  
Michaela Hau
Keyword(s):  
Sex Steroids ◽  
Steroid Receptors

Endocrinology of protochordates

2005 ◽  
Vol 83 (1) ◽  
pp. 225-255 ◽  
Author(s):  
Nancy M Sherwood ◽  
Bruce A Adams ◽  
Javier A Tello
Keyword(s):  
Sex Steroids ◽  
Large Scale ◽  
Steroid Receptors ◽  
Endocrine System ◽  
Egf Receptors ◽  
Vertebrate Lineage ◽  
Surface Receptors ◽  
Functional Studies ◽  
Full Complement ◽  
X Receptors

Large-scale gene duplications occurred early in the vertebrate lineage after the split with protochordates. Thus, protochordate hormones and their receptors, transcription factors, and signaling pathways may be the foundation for the endocrine system in vertebrates. A number of hormones have been identified including cionin, a likely ancestor of cholecytokinin (CCK) and gastrin. Both insulin and insulin-like growth hormone (IGF) have been identified in separate cDNAs in a tunicate, whereas only a single insulin-like peptide was found in amphioxus. In tunicates, nine distinct forms of gonadotropin-releasing hormone (GnRH) are shown to induce gamete release, even though a pituitary gland and sex steroids are lacking. In both tunicates and amphioxus, there is evidence of some components of a thyroid system, but the lack of a sequenced genome for amphioxus has slowed progress in the structural identification of its hormones. Immunocytochemistry has been used to tentatively identify a number of hormones in protochordates, but structural and functional studies are needed. For receptors, protochordates have many vertebrate homologs of nuclear receptors, such as the thyroid, retinoic acid, and retinoid X receptors. Also, tunicates have cell surface receptors including the G-protein-coupled type, such as β-adrenergic, putative endocannabinoid, cionin (CCK-like), and two GnRH receptors. Several tyrosine kinase receptors include two epidermal growth factor (EGF) receptors (tunicates) and an insulin/IGF receptor (amphioxus). Interestingly, neither steroid receptors nor a full complement of enzymes for synthesis of sex steroids are encoded in the Ciona genome. Tunicates appear to have some but not all of the necessary molecules to develop a vertebrate-like pituitary or complete thyroid system.

scholarly journals Minireview: Rapid Actions of Sex Steroids in the Endothelium

Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2411-2422 ◽  
Author(s):  
Renee W. Y. Chow ◽  
David J. Handelsman ◽  
Martin K. C. Ng
Keyword(s):  
Sex Steroids ◽  
Target Genes ◽  
Steroid Receptors ◽  
Classical Model ◽  
Time Lag ◽  
Signaling Cascades ◽  
Sex Steroid ◽  
Specific Response ◽  
Steroid Administration ◽  
Steroid Signaling

The endothelium is a dynamic interface between the blood vessel and the circulating blood that plays a pivotal role in vascular homeostasis. As such, studies on sex steroid regulation of endothelial function are critical to understanding the role of sex steroids in cardiovascular health and disease. The classical model of steroid action involves liganded steroid receptors binding to specific response elements on target genes to regulate gene transcription. In whole organisms, the time lag between steroid administration and observable effects produced by newly synthesized protein is typically in the order of hours to days. And yet, some effects of steroids, such as vasodilatation, occur within seconds to minutes of steroid administration. Studies in multiple cell types have also shown that steroids can cause the rapid initiation of multiple signaling cascades and second messenger systems, prompting investigations into alternate, transcription independent mechanisms of steroid action. Studies of the endothelium over the past two decades have revealed fundamental mechanisms in rapid sex steroid signaling. In particular, endothelium-dependent vasodilatation by estradiol-induced activation of endothelial nitric oxide synthase has proven to be an uniquely informative model to study sex steroid signaling via classical sex steroid receptors localized to the cell membrane. Despite the complexity of feedback and cross talk between rapid sex steroid signaling and other modes of steroid action, recent studies in this field are facilitating the development of steroidal drugs that selectively target the ability of sex steroids to initiate signaling cascades.

Role of molecular chaperones in steroid receptor action

2004 ◽  
Vol 40 ◽  
pp. 41-58 ◽  
Author(s):  
William B Pratt ◽  
Mario D Galigniana ◽  
Yoshihiro Morishima ◽  
Patrick J M Murphy
Keyword(s):  
Transcriptional Activation ◽  
Protein Trafficking ◽  
Steroid Receptors ◽  
Transcriptional Regulatory ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Receptor Action ◽  
Binding Cleft ◽  
Hsp 90

Unliganded steroid receptors are assembled into heterocomplexes with heat-shock protein (hsp) 90 by a multiprotein chaperone machinery. In addition to binding the receptors at the chaperone site, hsp90 binds cofactors at other sites that are part of the assembly machinery, as well as immunophilins that connect the assembled receptor-hsp90 heterocomplexes to a protein trafficking pathway. The hsp90-/hsp70-based chaperone machinery interacts with the unliganded glucocorticoid receptor to open the steroid-binding cleft to access by a steroid, and the machinery interacts in very dynamic fashion with the liganded, transformed receptor to facilitate its translocation along microtubular highways to the nucleus. In the nucleus, the chaperone machinery interacts with the receptor in transcriptional regulatory complexes after hormone dissociation to release the receptor and terminate transcriptional activation. By forming heterocomplexes with hsp90, the chaperone machinery stabilizes the receptor to degradation by the ubiquitin-proteasome pathway of proteolysis.

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