Studies on the mechanism of follicle-stimulating hormone-induced desensitization of Sertoli cell adenylyl cyclase in vitro.
When Sertoli cells were cultured in the presence of follicle-stimulating hormone (FSH), a time-and concentration-dependent desensitization of FSH-responsive adenylyl cyclase (AC) was observed. Maximal desensitization (80%) was attained after 6-9 h of incubation with FSH (10 micrograms/ml; NIH-FSH-S12). During 24 h of incubation the concentration of FSH causing a half-maximal desensitization was about 100 ng/ml. Removal of the hormone from the culture medium was associated with a gradual reappearance of the FSH response. Follicle-stimulating hormone-induced desensitization of Sertoli cell AC was specific for homologous hormone, since AC activation by isoproterenol was unaffected. Furthermore, AC activity of control and FSH-desensitized cells was equally activated by GTP and fluoride, showing that the interaction of the guanyl nucleotide regulatory (N) component with the catalytic subunit is not affected during FSH-induced desensitization. A loss in specific FSH binding was detected after 9 and 24 h of exposure to FSH, but not at shorter times of incubation. Desensitization of Sertoli cell AC to both FSH and isoproterenol stimulation could also be achieved by dibutyryl cyclic AMP (dbcAMP); however, a 30-40% desensitization required a high nucleotide concentration (1 mM) and a long incubation time (24 h). These results show that desensitization of Sertoli cell AC by FSH is associated with normal function of the N component, and precedes any significant loss in specific FSH binding sites. Furthermore, exogenous addition of dbcAMP (1 mM) did not cause the same effects on Sertoli cell AC as did FSH.
Le Gac
F
F
Attramadal
H
H
Jahnsen
T
T
Hansson
V
V
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004789:Enzyme Activation / Q000187:drug effects; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012708:Sertoli Cells / Q000201:enzymology*
D003994:Bucladesine; D006160:Guanosine Triphosphate; D005640:Follicle Stimulating Hormone; D000262:Adenylyl Cyclases; D007545:Isoproterenol