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11-deoxycorticosterone is a potent agonist of the rainbow trout (Oncorhynchus mykiss) mineralocorticoid receptor.
The teleost fish are thought to lack the mineralocorticoid hormone aldosterone but possess mineralocorticoid receptor (MR) homologs. Here we describe the characterization of two rainbow troutExpand
Structural determinants of ligand binding to the mineralocorticoid receptor
TLDR
The recent determination of the X-ray crystal structures of the LBD of the wild-type MR and MR(S810L), which is responsible for a familial form of hypertension, has made it possible to elucidate the peculiar mechanism of activation of MR( S810L) and established a clear structure/activity relationship for steroidal and non-steroidal MR antagonists. Expand
A New Mode of Mineralocorticoid Receptor Antagonism by a Potent and Selective Nonsteroidal Molecule*
TLDR
It is proposed that BR-4628 is a bulky antagonist that inactivates MR through a passive mechanism and represents the prototype of a new class of MR antagonists. Expand
Antagonism in the human mineralocorticoid receptor
TLDR
A new mechanism of antagonism is proposed in which the AF2‐AD core region is destabilized by the loss of contacts between the antagonist and the helix H12 region, proposed in the light of the hMR homology model. Expand
Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension
The S810L mutation within the human mineralocorticoid receptor (MR S810L) induces severe hypertension and switches progesterone from antagonist to agonist. Here we report the crystal structures ofExpand
Identification of Multiple Gene Mutations Accounts for a new Genetic Architecture of Primary Ovarian Insufficiency.
TLDR
Digenic findings in several cases suggest that POI is not a purely monogenic disorder and points to a role of digenicity, and a synergistic effect of several mutations may underlie the POI phenotype. Expand
Two Families with Normosmic Congenital Hypogonadotropic Hypogonadism and Biallelic Mutations in KISS1R (KISS1 Receptor): Clinical Evaluation and Molecular Characterization of a Novel Mutation
TLDR
It is shown that a novel loss-of-function mutation in the KISS1R gene can cause familial nCHH, revealing the crucial role of this amino acid in KISS 1R function, and the observed restoration of gonadotropin secretion by exogenous GnRH administration further supports, in humans, the hypothalamic origin of the gonadotropic deficiency in this genetic form of n CHH. Expand
Synergistic signaling by corticotropin-releasing hormone and leukemia inhibitory factor bridged by phosphorylated 3',5'-cyclic adenosine monophosphate response element binding protein at the Nur
TLDR
It is concluded that both CREB phosphorylation at Ser-133 and level of CREB expression are crucial in LIF-CRH synergism where CREB, without direct DNA binding, could improve the stability of Nur77 and STAT1-3 binding to POMC promoter and facilitate the recruitment of coactivators. Expand
A Structural Explanation of the Effects of Dissociated Glucocorticoids on Glucocorticoid Receptor Transactivation
TLDR
Overall, the findings provide some structural guidelines for the synthesis of potential new dissociated glucocorticoids with a better therapeutic ratio. Expand
Characterization of seven novel mutations on the HEXB gene in French Sandhoff patients.
TLDR
A rapid detection of the Sandhoff disease-causing alleles facilitating genetic counselling and prenatal diagnosis in at-risk families is reported. Expand
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