The action of luteinizing hormone on the testis.
Luteinizing hormone (LH) and human chorionic gonadotrophin (hCG) receptors are coupled to intracellular effector systems, most notably adenylate cyclase, through guanyl nucleotide-binding proteins or G-proteins. The molecular mechanism involved in the dynamic coupling of the LH/hCG receptor however, are not known. It has been postulated that receptor aggregation at the molecular level plays a critical role in this process. There have been attempts to understand the receptor association and dissociation phenomena at the molecular level. One of them involves the participation of the major histocompatibility complex (MHC) class I antigen in the mechanism of receptor activation and/or expression. One molecular basis for these mechanisms consists of a physical interaction between MHC proteins and receptors to form "compound receptors" able to transfer a hormonal signal to the cell. Using a photo-reactive probe we demonstrated that the LH/hCG receptors and the class I antigens are closely associated in the membrane. Thus, it is possible to form covalent complexes of hCG and class I antigens through the binding of the hormone to specific receptors. These findings imply that LH/hCG receptors and the MHC class I antigens may interact at the level of the plasma membrane in the mechanism of LH action. We also performed experiments using a single cell and limiting stimulation to a patch of membrane. The results stimulating the cell in a localized area suggested that even if all components are entirely free to float there is a constraint in the localization of the receptor, G-protein, and/or the effector, supporting the constraint dissociation model. Within a limited area subunits could dissociate, but they would not be free to diffuse throughout the membrane. Moreover the concept of compartmentalization that has been utilized to explain some inconsistencies in second-messenger action now can be proved by experimental design.
Neuman
I
I
Department of Biochemistry, School of Medicine, University of Buenos Aires, Argentina.
Solano
A R
AR
Paz
C
C
Mele
P
P
Cornejo Maciel
F
F
Lemos
J R
JR
Fernandez
H N
HN
Podesta
E J
EJ
D000818:Animals; D006063:Chorionic Gonadotropin / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007985:Leydig Cells / Q000378:metabolism* / Q000648:ultrastructure; D007986:Luteinizing Hormone / Q000502:physiology*; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D011974:Receptors, LH / Q000378:metabolism; D013737:Testis / Q000378:metabolism* / Q000648:ultrastructure
D006063:Chorionic Gonadotropin; D015395:Histocompatibility Antigens Class I; D011974:Receptors, LH; D007986:Luteinizing Hormone