Please use this identifier to cite or link to this item:
Title: Steroid binding sites in liver membranes: Interplay between glucocorticoids, sex steroids, and pituitary hormones
Authors: Fernández-Pérez, L. 
Flores-Morales, A. 
Chirino-Godoy, R. 
Díaz-Chico, J. C. 
Díaz-Chico, B. N. 
UNESCO Clasification: 32 Ciencias médicas
2415 Biología molecular
Keywords: Male-Rat Liver
Photoaffinity-Labeling Identification
Growth Factor-I
Gene-Expression, et al
Issue Date: 2008
Journal: Journal of Steroid Biochemistry and Molecular Biology 
Conference: 12th International Congress on Hormonal Steroids and Hormones and Cancer 
Abstract: Steroid hormones activate target cells through specific receptors that discriminate among ligands based upon recognition of distinct structural features. For most known steroids, membrane and nuclear receptors co-exist in many target cells. However, while the structure of the nuclear receptors and their function as transcriptional activators of specific target genes is generally well understood, the identity of the membrane receptors remains elusive. Using pharmacological and biochemical approaches, we are beginning to characterize receptors for glucocorticoids and anabolic-androgenic steroids in male rat liver membranes. Male rat liver endoplasmic reticulum contains two steroid binding sites which are functionally related and associated with a 90-134kDa oligomeric protein: (1) the low-affinity glucocorticoid binding site (LAGS), composed at least in part of two peptides (37 and 53 kDa) that bind glucocorticoids and (2) the stanozolol binding protein (STBP), composed at least in part of three peptides (22,31, and 55 kDa) that bind the synthetic androgen stanozolol. These steroid binding proteins have many properties different from those of classical nuclear receptors, with the salient differences being a failure to recognize "classical" ligands for nuclear receptors together with marked differences in biochemical properties and physiological regulation. The mechanism of interaction of glucocorticoids with the LAGS can be clearly distinguished from that with STBP. Moreover, STBP shows an extremely narrow pharmacological profile, being selective for ST and its analog, danazol, among more than 100 steroids and non-steroidal compounds that were assayed, including those that are able to displace glucocorticoids from the LAGS. The level of LAGS activity undergoes dramatic variations following changes from the physiological serum levels of thyroid hormones, glucocorticoids, GH, vitamin A, and E2. However, neither thyroid hormones nor GH have a critical role on STBP activity. The STBP is functionally related to LAGS. We have suggested a novel mechanism for STBP whereby membrane-associated glucocorticoid binding activity is targeted by stanozolol (and 16 beta-hydroxylated stanozolol): stanozolol modulates glucocorticoid activity in the liver through negative allosteric modulation of the LAGS resulting in an effective increase in classical GR-signaling by increasing glucocorticoid availability to the cytosolic GR.
ISSN: 0960-0760
DOI: 10.1016/j.jsbmb.2008.03.019
Source: Journal of Steroid Biochemistry and Molecular Biology[ISSN 0960-0760],v. 109, p. 336-343
Appears in Collections:Artículos
Show full item record

Google ScholarTM




Export metadata

Items in accedaCRIS are protected by copyright, with all rights reserved, unless otherwise indicated.