نتایج جستجو برای: gnrhr

تعداد نتایج: 235  

Journal: :Molecular endocrinology 1998
X Lin J A Janovick S Brothers M Blömenrohr J Bogerd P M Conn

Mammalian GnRH receptor (GnRHR) is unique among G protein-coupled seven-transmembrane segment receptors due to the absence of an intracellular C-terminal tail frequently important for internalization and/or desensitization of other G protein-coupled receptors. The recent cloning of nonmammalian (i.e. catfish, goldfish, frog, and chicken) GnRHRs shows that these contain an intracellular C termin...

2012
Christopher J. Caunt Rebecca M. Perett Robert C. Fowkes Craig A. McArdle

Gonadotropin-releasing hormone receptors (GnRHR) mediate activation and nuclear translocation of the extracellular signal regulated kinases 1 and 2 (ERK) by phosphorylation on the TEY motif. This is necessary for GnRH to initiate transcriptional programmes controlling fertility, but mechanisms that govern ERK targeting are unclear. Using automated microscopy to explore ERK regulation in single ...

Journal: :The Journal of clinical endocrinology and metabolism 2002
Jo Ann Janovick Guadalupe Maya-Nunez P Michael Conn

In the present study, we demonstrate pharmacological rescue (assessed by ligand binding and restoration of receptor coupling to effector) of five naturally occurring GnRH receptor (GnRHR) mutants (T(32)I, E(90)K, C(200)Y, C(279)Y, and L(266)R), identified from patients with hypogonadotropic hypogonadism, as well as rescue of other defective receptors intentionally manufactured with internal or ...

2017
Ellen R. Busby Nancy M. Sherwood

Gonadotropin-releasing hormone (GnRH) is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex...

Journal: :Molecular pharmacology 2007
Trudy A Kohout Qiu Xie Shelby Reijmers Kenneth J Finn Zhiqiang Guo Yun-Fei Zhu R Scott Struthers

Drugs that exhibit insurmountable antagonism are proposed to provide improved clinical efficacy through extended receptor blockade. Long-term suppression of the gonadotropin-releasing hormone receptor (GnRHR) is an important therapeutic approach for a number of sex hormone-dependent diseases. In this study, we describe the mechanism and structural components required for insurmountable activity...

Journal: :The Journal of pharmacology and experimental therapeutics 2011
Jo Ann Janovick Irina D Pogozheva Henry I Mosberg P Michael Conn

G protein-coupled receptors (GPCRs) play central roles in most physiological functions, and mutations in them cause heritable diseases. Whereas crystal structures provide details about the structure of GPCRs, there is little information that identifies structural features that permit receptors to pass the cellular quality control system or are involved in transition from the ground state to the...

Journal: :American journal of physiology. Endocrinology and metabolism 2013
Javier A Tello Trudy Kohout Rafael Pineda Richard A Maki R Scott Struthers Robert P Millar

The human GnRH receptor (GNRHR1) has a specific set of properties with physiological and pharmacological influences not appropriately modeled in laboratory animals or cell-based systems. To address this deficiency, we have generated human GNRHR1 knock-in mice and described their reproductive phenotype. Measurement of pituitary GNRHR1 transcripts from homozygous human GNRHR1 knock-in (ki/ki) mic...

Journal: :Endocrinology 2013
Delphine Burel Jian Hua Li Jean-Luc Do-Rego Ai Fen Wang Van Luu-The Georges Pelletier Yves Tillet Catherine Taragnat Hyuk Bang Kwon Jae Young Seong Hubert Vaudry

The sulfated neurosteroids pregnenolone sulfate (Δ(5)PS) and dehydroepiandrosterone sulfate (DHEAS) are known to play a role in the control of reproductive behavior. In the frog Pelophylax ridibundus, the enzyme hydroxysteroid sulfotransferase (HST), responsible for the biosynthesis of Δ(5)PS and DHEAS, is expressed in the magnocellular nucleus and the anterior preoptic area, two hypothalamic r...

Journal: :Proceedings of the National Academy of Sciences of the United States of America 2013
Jo Ann Janovick M David Stewart Darla Jacob L D Martin Jian Min Deng C Allison Stewart Ying Wang Anda Cornea Lakshmi Chavali Suhujey Lopez Shoukhrat Mitalipov Eunju Kang Hyo-Sang Lee Pulak R Manna Douglas M Stocco Richard R Behringer P Michael Conn

Mutations in receptors, ion channels, and enzymes are frequently recognized by the cellular quality control system as misfolded and retained in the endoplasmic reticulum (ER) or otherwise misrouted. Retention results in loss of function at the normal site of biological activity and disease. Pharmacoperones are target-specific small molecules that diffuse into cells and serve as folding template...

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