+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

The glucocorticoid properties of the synthetic steroid pregna-1,4-diene-11beta-ol-3,20-dione (deltaHOP) are not entirely correlated with the steroid binding to the glucocorticoid receptor

, : The glucocorticoid properties of the synthetic steroid pregna-1,4-diene-11beta-ol-3,20-dione (deltaHOP) are not entirely correlated with the steroid binding to the glucocorticoid receptor. Molecular and Cellular Endocrinology 149(1-2): 207-219

The natural steroid 11beta-hydroxyprogesterone is not only a modulator of 11beta-hydroxy-steroid dehydrogenase activity, but also an efficient inducer of tyrosine aminotransferase activity in hepatocytes. In contrast with the low affinity for the mineralocorticoid receptor. 11beta-hydroxyprogesterone binds well to both the glucocorticoid receptor and the carrier protein transcortin. It is accepted that the introduction of a 1:ene double bond into 3-keto 4:ene steroids increases the glucocorticoid potency, so that 3-keto-1,4:diene steroids show improved chemical stability and are more potent glucocorticoids than their respective 4:ene analogs. The steroid pregna-1,4-diene-11beta-ol-3,20-dione (deltaHOP) had previously been described as an anti-inflamatory compound and an inhibitor of macromolecular biosynthesis in thymocytes and lymphocytes. In such studies, deltaHOP also exhibited some particular glucocorticoid properties which made it attractive as a tool for the study of the mechanism of action of glucocorticoids. In the present paper we show that deltaHOP possesses some classical biological actions of glucocorticoids such as deposition of glycogen in rat liver, induction of TAT activity in hepatocytes, and inhibition of the uptake of leucine and thymidine by thymocytes. It also exhibits minimal sodium-retaining properties. Consistent with these biological effects, deltaHOP shows a 70 times lower relative binding affinity for the mineralocortioid receptor than aldosterone, but a reasonable affinity for the glucocorticoid receptor, and is as efficient as dexamethasone in dissociating the 90 kDa heat shock protein from the glucocorticoid receptor heterocomplex. However, the inhibition of the uptake of amino acids and nucleotides observed in the presence of deltaHOP is not efficiently blocked when thymocytes are coincubated in the presence of steroids with known antiglucocorticoid activity. deltaHOP is similarly inefficient in inducing chloramphenicol-acetyl transferase activity in cells transfected with a plasmid that possesses two canonical glucocorticoid-responsive elements. Unlike most glucocorticoids, deltaHOP does not induce the fragmentation of DNA in a regular pattern characteristic of apoptosis and it does not reduce thymus weight. This unusual dissociation of glucocorticoid parameters makes deltaHOP a useful tool to discriminate between mechanisms of action by which steroids can exert their biological effects.


PMID: 10375032

Other references

Anonymous, 1977: The status of continuing education: voluntary and mandatory. American Journal of Nursing 77(3): 410-416

Nankar, R.P.; Doble, M., 2017: Hybrid drug combination: Anti-diabetic treatment of type 2 diabetic Wistar rats with combination of ellagic acid and pioglitazone. Pioglitazone is an effective drug for the treatment of type 2 diabetes. The drug was suspended from Indian market in June 2013 due to the risk of bladder cancer but was reintroduced in July 2013 because its benefits outweighed the risks. The risks...

Griesmayer, E.; Auberger, T., 2004: The status of MedAustron. This paper describes the status of the design study of the Austrian Ion Therapy and Cancer-Research Centre Project MedAustron. This work was performed during the last two years by the MedAustron study group. The team was spread out over several re...

Thuillet, A-C.; Bataillon, T.; Sourdille, P.; David, J.L., 2003: Factors affecting polymorphism at microsatellite loci in bread wheat [ Triticum aestivum (L.) Thell]: effects of mutation processes and physical distance from the centromere. The effects of factors known to influence the level of polymorphism at microsatellite loci were studied using 99 markers and seven lines of bread wheat. Mutational factors as well as indirect selective events shape diversity at these loci. Theory...

Mayer, K., 1942: Report on the acceptability of the whole grain bread baked by the Institute of Baking, Berlin, in studies during the spring of 1941. The bread was made from whole rye with the addition of an unknown quantity of wheat flour. It was sent from Berlin to Konigsberg once weekly and kept well. It was tested by 25 healthy persons and 50 patients with gastro-intestinal disease. Each re...

Murota, J.; Sakuraba, M.; Tillack, B., 2011: Atomically controlled processing in silicon-based CVD epitaxial growth. One of the main requirements for Si-based ultrasmall device is atomic-order control of process technology. Here, we show the concept of atomically controlled processing for group IV semiconductors based on atomic-order surface reaction control in...

Acosta, A.C.; Uffo, O.; Sanz, A.; Ronda, R.; Osta, R.; Rodellar, C.; Martin-Burriel, I.; Zaragoza, P., 2013: Genetic diversity and differentiation of five Cuban cattle breeds using 30 microsatellite loci. Conservation and improvement strategies in farm animals should be based on a combination of genetic and phenotypic characteristics. Genotype data from 30 microsatellites were used to assess the genetic diversity and relationships among five Cuban...

Hurr, K.; Kemp, B.; Silver, S.A.; el-Naggar, A.K., 1996: Microsatellite alteration at chromosome 3p loci in neuroendocrine and non-neuroendocrine lung tumors. Histogenetic and clinical relevance. Although chromosome 3p regions are the most frequent site for genetic alterations in small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), the extent of such abnormality in carcinoid tumors remained to be investigated. Moreov...

Griffe, O., 2002: Recognition of the burn centers in the French health system. Soins; la Revue de Reference Infirmiere: 50-50

George, C.F., 1975: Problems in assessing beta-adrenoceptor antagonism in man. British Journal of Clinical Pharmacology 2(1): 3-4