Characterization of gonadotropin-sensitive adenylate cyclase activity in human testis: uncoupling of the receptor-cyclase complex by specific hormonal antagonist.
Basal and gonadotropin stimulated adenylate cyclase activity was assessed in testicular tissues obtained from men (20-80 years). A disparity was observed in the gonadotropin responsiveness of the human testicular adenylate cyclase system to hFSH and hCG stimulation. Of the tissues analyzed, 61% were FSH responsive and 22% showed low response to hCG. Forskolin, a diterpene which activates adenylate cyclase by a receptor independent mechanism, stimulated adenylate cyclase activity in the gonadotropin unresponsive tissues. This suggests that the tissue unresponsiveness is due to an uncoupling of the catalytic subunit of the adenylate cyclase. Several functional properties of the FSH responsive human testicular adenylate cyclase were investigated. hFSH and oFSH stimulated the enzyme activity in a concentration dependent manner. However, the hormone (DG-oFSH) in which 80% of the carbohydrate residues had been removed was inactive, despite its good binding ability to the FSH receptor. hFSH stimulated adenylate cyclase activity was inhibited by DG-oFSH but not by DG-hCG (deglycosylated hCG). The data demonstrates the existence of specific FSH and LH(hCG) receptors in human testicular membranes. The FSH receptors in some tissues are coupled to adenylate cyclase. The link between the FSH receptor and adenylate cyclase may be uncoupled in the presence of the deglycosylated form of oFSH resulting in a loss of hormone response.
Berman
M I
MI
Anand-Srivastava
M B
MB
Sairam
M R
MR
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000328:Adult; D000368:Aged; D006063:Chorionic Gonadotropin / Q000378:metabolism; D005576:Colforsin; D004224:Diterpenes / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D006150:Guanine Nucleotides / Q000494:pharmacology; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D008670:Metals; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011962:Receptors, FSH; D011974:Receptors, LH; D013329:Structure-Activity Relationship; D013347:Subcellular Fractions / Q000502:physiology; D013737:Testis / Q000201:enzymology*
D006063:Chorionic Gonadotropin; D004224:Diterpenes; D006150:Guanine Nucleotides; D008670:Metals; D011956:Receptors, Cell Surface; D011962:Receptors, FSH; D011974:Receptors, LH; D005576:Colforsin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D000262:Adenylyl Cyclases; D005459:Fluorides