An explanation for the disparate effects of synthetic peptides corresponding to human follicle-stimulating hormone beta-subunit receptor binding regions (33-53) and (81-95) and their serine analogs on steroidogenesis in cultured rat Sertoli cells.
We have recently reported that synthetic peptide amides corresponding to regions of human FSH beta-subunit, hFSH-beta-(33-53) and hFSH-beta-(81-95), bind to receptor and stimulate estradiol biosynthesis by cultured rat Sertoli cells. Because of experimental difficulties caused by the presence of free sulfhydryl groups in these peptides, synthetic analogs were prepared in which all Cys residues were replaced with Ser. These analogs, [Ser-51]-hFSH-beta-(33-53) and [Ser-82, 84, 87, 94]-hFSH-beta- (81-95), also bound to receptor but did not stimulate estradiol biosynthesis by cultured rat Sertoli cells. In order to explain this observation, we compared the effects of hFSH-beta-(33-53) and hFSH-beta-(81-95) and their Ser analogs on another recently recognized effect of FSH in Sertoli cells, namely its ability to promote influx of extracellular calcium. We and others have shown that estradiol biosynthesis by these cells is markedly decreased in the presence of high intracellular calcium. Cys-containing hFSH-beta-(33-53) and hFSH-beta-(81-95) did not increase influx of extracellular calcium over basal levels, whereas [Ser-51]-hFSH-beta-(33-53) and [Ser-82, 84, 87, 94]-hFSH-beta-(81-95) induced 2.8- and 1.8-fold increases, respectively. Cellular cAMP and estradiol biosynthesis in response to each Ser-substituted peptide were not significantly different from basal levels. Thus, the explanation for the observed disparate effects of Cys and Ser analog peptides on estradiol biosynthesis may be related to the ability of the Ser peptides to stimulate calcium entry but not cAMP accumulation in cultured rat Sertoli cells.
Grasso
P
P
Department of Biochemistry and Molecular Biology, Albany Medical College, New York 12208.
Crabb
J W
JW
Reichert
L E
LE
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005640:Follicle Stimulating Hormone / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D037201:Follicle Stimulating Hormone, beta Subunit; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011962:Receptors, FSH / Q000378:metabolism*; D012708:Sertoli Cells / Q000378:metabolism*; D013329:Structure-Activity Relationship
D037201:Follicle Stimulating Hormone, beta Subunit; D010446:Peptide Fragments; D011962:Receptors, FSH; D005640:Follicle Stimulating Hormone; D002118:Calcium