Cloning, sequencing, and expression of human gonadotropin releasing hormone (GnRH) receptor.

Gonadotropin releasing hormone is a hypothalamic decapeptide that stimulates the release of gonadotropic hormones from the anterior pituitary gland. Therapeutically, the human pituitary GnRH receptor is the target of agonists used in the suppression of prostate cancer. Here we report the isolation of a cDNA representing this receptor. It encodes a protein with a transmembrane topology similar with that of other G protein-coupled, 7-transmembrane receptors. Binding studies of the cloned receptor demonstrate high affinity and pharmacological properties similar with the native human pituitary GnRH receptor. Northern blot and reverse transcriptase/PCR analysis revealed that its mRNA is expressed in pituitary, ovary, testis, breast, and prostate but not in liver and spleen. Availability of a human GnRH receptor cDNA should permit the design of improved analogs for therapeutic applications.

[1]  T. Attwood,et al.  Multiple sequence alignment of protein families showing low sequence homology: a methodological approach using database pattern-matching discriminators for G-protein-linked receptors. , 1991, Gene.

[2]  R. Barbieri.  Clinical applications of GnRH and its analogues , 1992, Trends in Endocrinology & Metabolism.

[3]  K. Eidne,et al.  Gonadotropin-releasing hormone receptors in human pituitary: ligand structural requirements, molecular size, and cationic effects. , 1985, The Journal of clinical endocrinology and metabolism.

[4]  T. Plant,et al.  Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone , 1978 .

[5]  K. Catt,et al.  Binding affinity and biological activity of gonadotropin releasing hormone agonists in isolated pituitary cells. , 1982, Endocrinology.

[6]  J. D. Neill,et al.  Differential expression of angiotensin II receptor subtype mRNAs (AT-1A and AT-1B) in the brain. , 1992, Biochemical and biophysical research communications.

[7]  L. Musgrove,et al.  Angiotensin II type-1 receptor subtype cDNAs: differential tissue expression and hormonal regulation. , 1992, Biochemical and biophysical research communications.

[8]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[9]  P. Conn,et al.  Distribution of gonadrotropin releasing hormone agonist binding sites in the rat central nervous system , 1988, Brain Research.

[10]  J. Richards,et al.  Ovarian gonadotropin-releasing hormone (GnRH) receptors: characterization, distribution, and induction by GnRH. , 1981, Endocrinology.

[11]  S. Sealfon,et al.  Cloning and functional expression of a mouse gonadotropin-releasing hormone receptor. , 1992, Molecular endocrinology.

[12]  P. Conn,et al.  Molecular mechanism of gonadotropin releasing hormone action. II. The effector system. , 1988, Endocrine reviews.

[13]  K. Catt,et al.  Receptor-binding affinity of gonadotropin-releasing hormone analogs: analysis by radioligand-receptor assay. , 1980, Endocrinology.