Corticotropin positively regulates its own receptors and cAMP response in cultured bovine adrenal cells.
Bovine fasciculata adrenal cells contain specific high-affinity (KD approximately 2.3 +/- 0.4 x 10(-10) M) and low-capacity (1910 +/- 300 sites per cell) corticotropin (ACTH) receptors. Pretreatment of cells with ACTH, caused in a time-(maximum effect at 48 hr) and dose-(ED50 approximately 10(-11) M, Vmax = 10(-10) to 10(-9) M) dependent manner an increase in ACTH binding. This was due to a 4-fold increase in the number of binding sites without modification of the binding affinity. The same pretreatment also enhanced the cAMP response to further ACTH stimulation in a dose-dependent manner (ED50 approximately 10(-11) M) and to a lesser extent the response to forskolin. However, pretreatment with higher concentrations of ACTH (10(-8) M) reduced the binding and the cAMP response when compared to the effect of 10(-9) M. These ACTH effects, which were mimicked by 8-bromoadenosine 3',5'-cyclic monophosphate, required de novo protein synthesis. Pretreatment with 10(-13) to 10(-11) M ACTH also enhanced the steroidogenic responsiveness to further hormonal stimulation. However, at higher concentrations the hormone induced an apparent steroidogenic desensitization that was probably related to a depletion of endogenous cholesterol, since cortisol production in the presence of 22-(R)-hydroxycholesterol was increased. Neither angiotensin-II nor atrial natriuretic factor alone modified ACTH receptors, but angiotensin-II partially blocked the stimulatory effect of ACTH. Thus, ACTH is one of the few polypeptide hormones having a positive trophic effect on its own receptors and target-cell responsiveness.
Penhoat
A
A
Institut National de la Santé et de la Recherche Médicale, Hôpital Debrousse, France.
Jaillard
C
C
Saez
J M
JM
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D007700:Kinetics; D018043:Receptors, Corticotropin; D011979:Receptors, Pituitary Hormone / Q000187:drug effects / Q000378:metabolism*
D018043:Receptors, Corticotropin; D011979:Receptors, Pituitary Hormone; D000804:Angiotensin II; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009320:Atrial Natriuretic Factor; D000324:Adrenocorticotropic Hormone; D003513:Cycloheximide; D000242:Cyclic AMP