Synthetic alpha-subunit peptides stimulate testosterone production in vitro by rat Leydig cells.
The glycoprotein hormones (LH, hCG, FSH, and TSH) have a common 92-amino acid alpha-subunit which is noncovalently linked to a hormone-specific beta-subunit. Synthetic peptides of the alpha-subunit have been shown to inhibit binding of [125I]iodo-hCG to rat ovarian membrane and [125I]iodo-TSH to human thyroid membrane preparations. Synthetic overlapping peptides of the alpha-subunit of hCG were prepared by solid phase techniques and tested in a standard in vitro rat Leydig cell bioassay. Three regions in the alpha-subunit (alpha 1-15, alpha 30-45, and alpha 71-85) were found to stimulate testosterone production. All three regions correlate with inhibition of hCG binding to ovarian receptors, but subtle differences exist between the binding sites and effector sites. These data indicate that the glycoprotein alpha-subunit has intrinsic bioactivity.
Erickson
L D
LD
Department of Obstetrics and Gynecology and Biochemistry and Molecular Biology, Mayo Medical School, Rochester, Minnesota 55905.
Rizza
S A
SA
Bergert
E R
ER
Charlesworth
M C
MC
McCormick
D J
DJ
Ryan
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000378:metabolism; D002942:Circular Dichroism; D005260:Female; D015292:Glycoprotein Hormones, alpha Subunit / Q000494:pharmacology*; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011487:Protein Conformation; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013739:Testosterone / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; D015292:Glycoprotein Hormones, alpha Subunit; D010446:Peptide Fragments; D013739:Testosterone