Unique properties of the follicle-stimulating hormone- and cholera toxin-sensitive adenylyl cyclase of immature granulosa cells.
Previous studies have shown that the adenylyl cyclase of intact granulosa cells from immature porcine follicles has a uniquely prolonged responsiveness to FSH and an atypically poor responsiveness to cholera toxin relative to other cells. The present studies were designed to determine if these characteristics were due to unique regulation of the adenylyl cyclase activation process by Mg2+ and guanine nucleotides. GTP and Mg2+ enhanced adenylyl cyclase activity in the absence and presence of FSH in a manner similar to that in other systems. For example, GTP and Mg2+ increased the maximal velocity rather than the sensitivity of the cyclase to GTP and Mg2+. However, several unique properties distinguish the FSH-sensitive adenylyl cyclase from other hormonally activated adenylyl cyclases. First, FSH did not increase the sensitivity of the enzyme to Mg2+; thus the apparent Km for Mg2+ remained nonphysiologically high in the presence of FSH. Second, FSH was only one fourth as effective as NaF in activating the enzyme. Third, maximal activity attained in the presence of NaF was very low relative to that in other cells. Fourth, even in the presence of exogenous NAD+, cholera toxin activated adenylyl cyclase only as well as FSH rather than as well as NaF. Fifth, instead of causing maximal activation in the absence of stimulator, guanyl-5'-ylimidodiphosphate enhanced by almost 2-fold basal, FSH-activated, and cholera toxin-activated adenylyl cyclase. The inability of either guanyl-5'-ylimidodiphosphate or cholera toxin alone to cause maximal activation of the guanine nucleotide-binding protein, as reflected by cyclase activity, indicates that guanine nucleotide binding in the absence of hormone or cholera toxin is limiting.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000201:enzymology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D015636:Magnesium Chloride; D012969:Sodium Fluoride / Q000494:pharmacology; D013552:Swine
D000067956:Adenylyl Cyclase Inhibitors; D015636:Magnesium Chloride; D006165:Guanylyl Imidodiphosphate; D004533:Egtazic Acid; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D012969:Sodium Fluoride; D005640:Follicle Stimulating Hormone; D002772:Cholera Toxin; D004492:Edetic Acid; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D008274:Magnesium