Multiple regulatory elements in the human GnRH receptor gene

Rp, Millar

doi:10.1530/eje.0.1370118

Cited by 4 publications

(2 citation statements)

References 12 publications

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“…Since the GnRHR gene is highly regulated by GnRH itself and by gonadal steroids and peptides (29), selective forces may have favored low basal expression and selected against more highly expressing sequences.…”

Section: Discussionmentioning

confidence: 99%

A single amino acid substitution in transmembrane helix VI results in overexpression of the human GnRH receptor

Myburgh

Pawson

Davidson

et al. 1998

European Journal of Endocrinology

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Objective: Construction of constitutively active mutants of the GnRH receptor, a member of the Gprotein coupled receptor superfamily, would facilitate investigation of the mechanism of receptor activation. Design: Point mutations were introduced in the human GnRH receptor in positions corresponding to those which caused constitutive activity in other G-protein coupled receptors. The effects of these mutations on ligand binding, receptor intracellular signaling and receptor expression were determined. Methods: Wild type and mutated receptor cDNAs were expressed in COS-1 cells. Basal and agoniststimulated inositol phosphate production and ligand binding were determined. In addition, receptor mRNA levels, cell surface receptor stability and rate of internalization were measured. Results and conclusions: Although none of the mutant receptors exhibited constitutive activity, mutation of Phe-272 in transmembrane helix VI to Leu increased cell surface receptor numbers, with unchanged affinities for radiolabeled agonist, superagonist and antagonist peptides compared with wild type receptor. The cell surface receptor stability and rate of internalization were similar for wild type and F272L GnRH receptors. Thus a single amino acid mutation in transmembrane helix VI causes an increase in cell surface receptor numbers, which appears to result from an increased rate of receptor protein translation, processing or insertion into membranes.

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Section: Discussionmentioning

confidence: 99%

A single amino acid substitution in transmembrane helix VI results in overexpression of the human GnRH receptor

Myburgh

Pawson

Davidson

et al. 1998

European Journal of Endocrinology

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show abstract

“…We read with interest the article by Kakar (1) and the commentary by Miller (2) in the European Journal of Endocrinology, which showed the diversity and species speci®city of the regulatory elements in the gonadotropin-releasing hormone receptor (GnRHR) gene and reviewed the important role of GnRHR gene regulation in the control of the hypothalamic±pituitary±gonadal axis respectively. Thus we hypothesized that polymorphism(s) in the regulatory region in the GnRHR gene could be a genetic factor that in¯uences the timing of the onset of puberty.…”

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confidence: 99%