Estradiol treatment decreases the lipolytic responses of hamster white adipocytes through a reduction in the activity of the adenylate cyclase catalytic subunit.
After 5 days of daily administration of 10 micrograms estradiol to 6-week-old male hamsters, the in vitro maximal lipolytic and cAMP responses of white adipocytes to isoproterenol, epinephrine, ACTH, and theophylline were reduced by one half, with no change in the sensitivity of these responses. In contrast, the antilipolytic response to the alpha 2-adrenergic agonist clonidine was unimpaired. beta-Adrenergic receptor number and affinity, assessed in intact cells with [3H]CGP-12177 binding, showed no difference between control and estradiol-treated hamsters. In adipocyte membranes from estradiol-treated hamsters, maximal adenylate cyclase responses to Mn2+, GTP alone or in combination with isoproterenol, ACTH, or fluoride were all decreased by 30-40% below the values found in controls, but the sensitivity of these responses was unaltered. The maximum velocity (Vmax) of adenylate cyclase was reduced by one half in estrogen-treated animals, but the Michaelis-Menten constant (Km) of the enzyme for ATP was unchanged. Finally, complementation of adipocyte membranes with solubilized human erythrocyte Ns failed to restore to control values the maximal adenylate cyclase response to isoproterenol plus guanosine 5'-[beta, gamma-imido]-triphosphate in the estradiol-treated hamsters. These results indicate that a defect in the catalytic subunit of adenylate cyclase is one of the mechanisms through which estradiol treatment reduces the lipolytic response of hamster white adipocytes.
D000067956:Adenylyl Cyclase Inhibitors; D000273:Adipose Tissue / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005990:Glycerol / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008647:Mesocricetus; D011412:Propanolamines / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013806:Theophylline / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; D004958:Estradiol; D006160:Guanosine Triphosphate; D000324:Adrenocorticotropic Hormone; D013806:Theophylline; D000242:Cyclic AMP; D007545:Isoproterenol; D003000:Clonidine; D005990:Glycerol; C033394:CGP 12177; D004837:Epinephrine