Studies on structure-function relationships of human choriogonadotropins with C-terminally shortened alpha-subunits. II. Stimulation of adenylate cyclase activity and depletion of cytochrome P-450 in the rat testis.
Human choriogonadotropin (hCG) analogues, containing the native beta-subunit and alpha-subunits enzymatically shortened by 2-3 amino acid residues, were used for studying the influence of hCG on the content of microsomal progesterone-binding cytochrome P-450 in rat testis. When 2-3 residues have been removed from the alpha-subunit, the ability of the hormone analogue to stimulate adenylate cyclase of isolated rat Leydig cells was diminished by 55%. When the hCG analogue containing a des-(88-92)-alpha chain was applied, the residual activity of the adenylate cyclase was negligible. 18 h after administration to rats in vivo, the hormone species containing des-(Lys-91-Ser-92)-alpha or des-(90-92)-alpha, respectively, were found to have induced a decrease in microsomal cytochrome P-450 content with an effectiveness corresponding to their ability of stimulating the adenylate cyclase in vitro. However, when assayed 48 h after application, the desensitization of the microsomal cytochrome P-450 system had persisted in case of the hCG species containing a des-(90-92)-alpha chain but not in case of hCG consisting of des-(Lys-91-Ser-92)-alpha and a native beta-subunit. From these results, it is concluded that short-term effects of hCG on the microsomal content of progesterone-binding cytochrome P-450 are mediated by the stimulation of adenylate cyclase. In contrast, the long-lasting action of hCG on this system seems not to be exclusively mediated by the increase in intracellular cAMP.
Merz
W E
WE
Kühn-Velten
W N
WN
Sessler
M
M
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013737:Testis / Q000201:enzymology / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D003577:Cytochrome P-450 Enzyme System; D000242:Cyclic AMP; D000262:Adenylyl Cyclases