Mammalian Gonadotropin-Releasing Hormone (GnRH) Receptor Subtypes
| Autor: | Jimmy D. Neill |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
endocrine system
medicine.medical_specialty Physiology Gonadotropin-releasing hormone Biology Anterior pituitary Physiology (medical) Internal medicine medicine Enzyme-linked receptor Animals Humans RNA Messenger Receptor G protein-coupled receptor Haplorhini Sequence Analysis DNA General Medicine Gonadotropin secretion Endocrinology medicine.anatomical_structure Organ Specificity Interleukin-21 receptor Receptors LHRH hormones hormone substitutes and hormone antagonists Endocrine gland |
| Zdroj: | Archives of Physiology and Biochemistry. 110:129-136 |
| ISSN: | 1744-4160 1381-3455 |
| DOI: | 10.1076/apab.110.1.129.900 |
| Popis: | Mammalian gonadotropin-releasing hormone (GnRH I) is a hypothalamic decapeptide that governs gonadotropin secretion through interaction with its seven transmembrane (7TM), G protein-coupled receptor (GPCR) expressed by anterior pituitary cells. A second decapeptide, GnRH II, originally discovered in the chicken hypothalamus was recently reported to be expressed in the mammalian hypothalamus as well. A search of the recently-sequenced human genome identified a 7TM/GPCR on chromosome 1 that exhibited a higher identity with non-mammalian vertebrate GnRH II receptors (55%) than with the human GnRH I receptor (39%). Molecular cloning and nucleotide sequencing of this putative GnRH II receptor cDNA from monkey pituitary gland revealed a 379 amino acid receptor that, unlike the GnRH I receptor, possessed a C-terminal tail. Heterologous expression and functional testing of the receptor in COS-1 cells confirmed its identity as a GnRH II receptor: measurement of 3H-inositol phosphate accumulation revealed EC(50)s for GnRH II of 0.86 nM and for GnRH I of 337 nM. Ubiquitous tissue expression of GnRH II receptor mRNA was observed using a human tissue RNA expression array and a 32P-labeled antisense riboprobe representing the 7TM region of human GnRH II receptor cDNA. As predicted by the presence of its C-terminal tail, the GnRH II receptor was desensitized by GnRH II treatment whereas the naturally tail-less GnRH I receptor was not desensitized by GnRH I. Pharmacological analysis of the GnRH II receptor revealed that GnRH I 'superagonists' were more potent than GnRH I but less potent than GnRH II. Numerous GnRH I antagonists showed neither antagonistic nor agonistic activity with the GnRH II receptor. The functions of the GnRH II receptor are unknown but may include regulation of gonadotropin secretion, female sexual behavior, or tumor cell growth. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|