The Lutropin/Choriogonadotropin Receptor… 4 Years Later*

Abstract

A comparison of this review with the review on the LH/CG receptor that we published in this journal 4 yr ago (1) clearly shows that the field has advanced tremendously in this short period of time. Many of the questions that were unanswered then have now been conclusively answered. On the other hand, as is always the case, the new knowledge generated has also resulted in many new questions that are yet to be answered. Hopefully it is clear from this review that the knowledge and experimental tools generated during the last 4 yr have given us new ammunition to address such important issues as the elucidation of the structural determinants of the LH/CG receptor that are involved in the different functions of this receptor, as well as on the molecular bases of receptor activation, inactivation, and regulation. In fact, since we finished writing this review in September of 1992, we are certain that some of the questions left unanswered here will already have an answer in 1993 when this review is published.

Engineering the Human Thyrotropin Receptor Ectodomain from a Non-secreted Form to a Secreted, Highly Immunoreactive Glycoprotein That Neutralizes Autoantibodies in Graves' Patients' Sera

“…Remarkably, in contrast to TSH, hCG binds with high affinity to the isolated ectodomain of its cognate receptor, even when the latter lacks carbohydrate (reviewed in Ref. 60). The reason for this major difference between such closely related receptors is an enigma.…”

Extragonadal LH/hCG action—Not yet time to rewrite textbooks

“…LH/hCG-Rs are located in the ovary in theca cells, luteinizing granulosa cells and after ovulation in luteal cells, in the testis they are expressed in Leydig cells (Segaloff and Ascoli, 1993). Follicle-stimulating hormone (FSH) -R, in turn, is exclusively expressed in ovarian granulosa cells and testicular Sertoli cells (Simoni et al, 1997).…”

“…According to a generally accepted dogma, LH is secreted from the anterior pituitary gland under the stimulatory control of hypothalamic gonadotropin-releasing hormone (GnRH), and it acts by binding to its specific receptors (LH/hCG-R), which belong to the family of seven-times membrane spanning G-protein coupled receptors (McFarland et al, 1989;Ascoli et al, 2002). In gonads, the LH/hCG-Rs are situated in testicular Leydig cells and in ovarian theca, granulosa and luteal cells (Segaloff and Ascoli, 1993;Dufau, 1998). LH has two roles in the regulation of gonadal function, i.e.…”

SH3 Binding Domains in the Dopamine D4 Receptor

“…In some cases, as seen with the P-adrenergic receptor, deletion of part of the carboxyl-tenninal tail leads to improved G proteincoupling efficiency (Parker and Ross,199 1 ), increased basal activity (Parker and Ross, 199 1 ), or increased prorniscuity for different G protein-coupling (Schneider et al, 1994). Complete removal of the carboxyl-terminal tail f?om GPCRs results in the inactivation of the receptor (Sano et al, 1997;Segaloff and Ascoli, 1993). AlthUugh, this region is believed to play an important role in G protein selectivity, replacement of the carboxyl-teminal tail fiom related, but bctionally distinct receptors, as in the case of the a , and Pz-adrenergic receptor, is not suffisent to alter G protein binding (Liggett et al, 1991).…”