Distinct Efficacies for Two Endogenous Ligands on a Single Cognate Gonadoliberin Receptor

• Published in: European journal of biochemistry Vol. 243; no. 1‐2; pp. 134 - 140
• Main Authors: Tensen, Cornelis, Okuzawa, Koichi, Blomenröhr, Marion, Rebersi, Frank, Leurs, Rob, Bogerd, Jan, Schulz, Rüdiger, Goos, Henk
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.01.1997
• Subjects: Amino Acid Sequence; Animals; Base Sequence; cDNA; Cell Line; Chickens; Fishes - physiology; Gene Expression Regulation, Developmental; gonadoliberin receptor; Gonadotropin-Releasing Hormone - chemistry; Gonadotropin-Releasing Hormone - physiology; GTP‐binding‐protein‐coupled receptor; Humans; Inositol Phosphates - metabolism; Ligands; Molecular Sequence Data; pituitary; Promoter Regions, Genetic; Receptors, LHRH - physiology; Recombinant Proteins; transfection
• ISSN: 0014-2956; 1432-1033
• DOI: 10.1111/j.1432-1033.1997.0134a.x

A cDNA encoding a putative gonadoliberin receptor was cloned from the pituitary of the African catfish. Conceptual translation predicts a protein of 379 amino acids which shows typical characteristics of GTP‐binding‐protein‐coupled receptors. The isolated cDNA was stable expressed in human embryonic kidney (HEK) 293 cells which were used for studies on gonadoliberin‐activated second messenger systems (inositol phosphate production; increase in CAMP andor intracellular Ca2+). The isolated cDNA encoded a functional receptor, designated catfish gonadoliberin receptor (cfGnRH‐R), which had an amino acid sequence similarity of 38% with mammalian gonadoliberin receptors. In contrast to its mammalian counterparts which lack an intracellular carboxy‐terminal domain, the cfGnRH‐R contains an additional 49 amino acid residues. From the two endogenous gonadoliberins in African catfish, chicken gonadoliberin‐11 had a several hundredfold higher potency than catfish gonadoliberin to activate cfGnRH‐R‐associated second messenger systems in transfected HEK 293 cells. This is in line with the previously determined higher gonadotropin‐release capacity of chicken gonadoliberin‐I1 in catfish. Stimulation of second messenger systems with chicken gonadoliberin‐11, but not with catfish gonadoliberin, resulted in a biphasic effect and chicken gonadoliberin‐II led to a higher maximum stimulation than catfish gonadoliberin. Challenging cfGnRH‐R simultaneously with chicken gonadoliberin‐II and catfish gonadoliberin did not lead to additive effects. In contrast, two types of mutual inhibitory effects were recorded. These data indicate that a single cognate cfGnRH‐R couples with distinct efficacies to signal transduction systems upon stimulation by the two endogenous gonadoliberins which, in addition, may interact negatively.