Activation of the rat luteinizing hormone following substitution of treonine-413 with selective residues

The glycoprotein hormones lutropin (LH), follitropin (FSH) and thyrotropin (TSH) control the many functions of the ovaries, testes and thyroid (27). Humans have two lutropins, (hLH) and chorionic gonadotropin (hCG). hLH is secreted from the pituitary gland while hCG is a placental protein (27). It has been known since 1989 that the receptor for these lutropins is a G protein-coupled receptor (GPCR), which constitute the largest most-conserved superfamily of signaling molecules (42). High affinity hormone binding results from interactions between residues in the curved portion of the extracellular domain of the receptor and the groove in the hormone formed by the apposition of the second α-subunit loop and the first and third β-subunit loops. Most of the remainder of the hormone is found in the large space between the arms of the extracellular domain and makes few, if any, additional specific contacts with the receptor needed for high affinity binding. Signal transduction is caused by steric or other influences of the hormone on the distance between the arms of the extracellular domain, an effect augmented by the oligosaccharides. Because the extracellular domain is coupled at multiple sites to the transmembrane domain, the change in conformation of the extracellular domain is relayed to the transmembrane domain and subsequently to the cytoplasmic surface of the plasma membrane. Here I will discuss several mutations made of the LHR amino acid Threonine 413 (T413). These six mutations were analyzed by hCG binding and cAMP assays. Since hCG is capable of stimulating steriodogenesis and cyclic AMP formation in the rat testicular tissues (28), it was important that we looked at not only the ability of the mutants created to bind hCG but also their effects on cAMP activation. It is important to study this particular amino acid because it is highly conserved over many species and the unique nature of this residue has not been investigated to our knowledge.M.S.Includes abstractIncludes bibliographical referencesby Nicole Lynn Arnol