Steroidogenic activity of synthetic hybrid molecules composed of human chorionic gonadotropin and either the A or B chain of lectin ricin or horseradish peroxidase.
Human chorionic gonadotropin (hCG) is a glycoprotein consisting of noncovalently bound alpha- and beta-subunits which shows hormonal activity (stimulatory effect on testosterone production) toward rat Leydig cells. To modify the hormonal activity of hCG, hybrid molecules composed of hCG and other glycoproteins, either the A or B chain of lectin ricin (hCG-A and hCG-B) through disulfide bridges and horseradish peroxidase (hCG-HRP) through Schiff's base, were synthesized. Hormonal activity and the effect of these hybrids on [125I]hCG binding to rat Leydig cells were compared to those of native hCG. Modification of hCG resulted in a significant decrease in hormonal activity for hCG-HRP but not for hCG-A to approximately 1/100 and 1/10 that of native hCG, respectively. On the other hand, hCG-B unexpectedly showed hormonal activity similar to that of native hCG. These hybrids inhibited the binding of 125I-labeled hCG to rat Leydig cells with potencies of 1/10, 1/100 and 1/500 that of hCG for hCG-B, hCG-A and hCG-HRP, respectively. These results indicate that the B chain of ricin, the active component hCG-B, participated in stimulating testosterone production according to its own nature. Data which indicate that hybrids consisting of hCG subunits and the B chain of ricin (alpha-B and beta-B) stimulated testosterone significantly more than hybrids consisting of hCG subunits and A chain (alpha-A and beta-A) support the above finding.(ABSTRACT TRUNCATED AT 250 WORDS)
Sakai
A
A
Department of Biochemistry, School of Clinical Pharmaceutical Sciences, Nagasaki University, Japan.
Sakakibara
R
R
Ohwaki
K
K
Ishiguro
M
M
D000818:Animals; D006063:Chorionic Gonadotropin / Q000737:chemistry / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D006735:Horseradish Peroxidase / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012276:Ricin; D013256:Steroids / Q000096:biosynthesis*; D013268:Stimulation, Chemical; D013739:Testosterone / Q000096:biosynthesis
D006063:Chorionic Gonadotropin; D013256:Steroids; D013739:Testosterone; D012276:Ricin; D000242:Cyclic AMP; D006735:Horseradish Peroxidase