Date Available


Year of Publication


Document Type



Arts and Sciences



First Advisor

Tae H. Ji


The Luteinizing hormone receptor (LHR) belongs to the G protein-coupled receptor family, asdo the other glycoprotein hormone receptors for FSH, TSH, and CG. The LHR comprises twohalves of ~350 amino acids: an extracellular hormone binding exodomain and a seventransmembrane-spanning endodomain responsible for signal generation. Hormone binds to theexodomain with high affinity, and the resulting conformational changes in thehormone/exodomain complex modulate the endodomain to generate hormone signals. Hormonebinding to an LHR produces hormonal signals (cis-activation), but it is not known whether aliganded LHR could activate other unoccupied LHRs (trans-activation). The LHR activates bothadenylyl cyclase and phospholipase C??. This dissertation shows that trans-activation of the LHRleads to the activation of adenylyl cyclase to induce cAMP but not to the activation ofphospholipase C?? to induce the inositol phosphate signaling. Trans-activation offers amechanism of signal amplification at the receptor level and also provides a mechanism ofmultiple signal generation for a liganded LHR to cis-activate phospholipase C?? and transactivateadenylyl cyclase. Also coexpression of Gi2 with a constitutively activating LHR(Asp578Gly), the most common mutation of male-limited precocious puberty, shows that Gi2could completely inhibit cAMP induction by the LHR mutant. Experiments using the carboxylterminal region of G protein ?? subunits demonstrate that LHR has overlapping binding sites forG?? subunits Gs and Gi2.