The sites of action and mechanisms by which gonadal steroids regulate gonadotrophin-releasing hormone (GnRH) in domestic animals remain largely unknown. This review summarises information gained from sheep regarding the distribution of the gonadal steroid receptors in the brain, the neurochemical identity and the projections of these steroid receptor-containing neurones. The cells in the hypoth...

The presence of a thiol in the steroid binding cavity of glucocorticoid receptors has recently been proved by our affinity labeling of Cys-656 in the steroid binding domain of rat receptors (Simons, s. s., Jr., Pumphrey, J. G., Rudikoff, S., and Eisen, H. J. (1987) J. Biol. Chem. 262,9676-9680). Studies with the sterically small, thiol-specific reagent methyl methanethiolsulfonate (MMTS) now re...

Neurosteroids positively and negatively modulate gamma-aminobutyric acid (GABA)(A) receptors and glutamate receptors, which underlie most fast inhibition and excitation in the central nervous system. We report the identification of a neuroactive steroid, (3 alpha,5 beta)-20-oxo-pregnane-3-carboxylic acid (3 alpha 5 beta PC), with unique cellular actions. 3 alpha 5 beta PC positively modulates G...

GABAA receptors are a pivotal inhibitory influence in the nervous system, and modulators of the GABAA receptor are important anesthetics, sedatives, anticonvulsants, and anxiolytics. Current views of receptor modulation suggest that many exogenous drugs access and bind to an extracellular receptor domain. Using novel synthetic steroid analogs, we examined the access route for neuroactive steroi...

A rapid method for simultaneous preparation of cytosol and nuclear estrogen (E) and progestin (P) receptors and their in vitro determination is described. The method was applied to several uterine or ovarian surgical specimens to evaluate their steroid hormone "dependence". The results suggest that low cytoplasmic E receptor levels (ERc) are associated with higher nuclear E receptor (ERn) level...

Background: Androgens are critical steroid hormones in progression of spermatogenesis process and determine the male phenotype that their actions are mediated by the androgen receptor (AR), a member of the nuclear receptor superfamily. In the Androgen receptor, transactivation domain encoded by exon 1, DNA binding domain encoded by exons 2 and 3, hinge region encoded by part of exon 4, and C-te...

Treatment of rat liver cytosol with hydrogen peroxide (H2O2) or sodium molybdate (MoO4(2-)) inhibits thermal inactivation of glucocorticoid receptor steroid-binding capacity at 25 degrees C. Dithiothreitol (DTT) prevents the stabilization of receptors by H2O2. Heating (25 degrees C) of immune pellets formed by immunoadsorption of L-cell murine glucocorticoid receptor complexes to protein-A-Seph...

Glucocorticoid response in target cells closely correlates with glucocorticoid receptor (GR) level. We have compared the localization of GR (by immunocytochemistry) and GR mRNA levels (by in situ hybridiza tion) in steroid-sensitive and steroid-resistant subclones derived from the human CEM lymphoid cell line. In addition, GR was localized in lymphoid cells from patients with various hematologi...

Gonadal steroid hormones act in the brain to elicit changes in gene expression that result in profound effects on behavior and physiology. A variety of in vitro studies indicate that nuclear receptor coactivators are required for efficient transcriptional activity of steroid receptors. Two nuclear receptor coactivators, steroid receptor coactivator-1 (SRC-1) and cAMP response element binding pr...

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 hs...