A study of mechanisms by which adrenocorticotropic hormone maintains adrenal steroidogenic responsiveness.

Following hypophysectomy in the rat, there was a progressive decline in the rate of adrenal protein synthesis in vivo during the ensuing 24-48 hr, and an accompanying decrease in the acute corticosterone secretory response to an intravenous injection of ACTH. There was a similar decrease in the in vitro conversion of Delta(5)-pregnenolone, progesterone, and deoxycorticosterone to corticosterone. These in vivo and in vitro effects of hypophysectomy could be reversed by the administration of depot ACTH for an additional 7 hr period. However, if cycloheximide, an inhibitor of protein synthesis, was administered concomitantly with the depot ACTH, then the restorative actions of ACTH on the steroid biosynthetic pathway were prevented. These experiments suggest that ACTH maintains not only the general structure of the adrenal cortex, but also the level of the steroid biosynthetic mechanism, through its effects on adrenal protein synthesis.

[1]  R. N. Dexter,et al.  Inhibition of adrenal corticosteroid synthesis by aminoglutethimide: studies of the mechanism of action. , 1967, The Journal of clinical endocrinology and metabolism.

[2]  L. Garren,et al.  Studies on the role of protein synthesis in the regulation of corticosterone production by adrenocorticotropic hormone in vivo. , 1965, Proceedings of the National Academy of Sciences of the United States of America.

[3]  S. Koritz,et al.  Identity of the Site of Action of 3',5'-Adenosine Monophosphate and Adrenocortocotropic Hormone in Corticosteroidogenesis in Rat Adrenal and Beef Adrenal Cortex Slices* , 1965 .

[4]  R. Farese.  CHANGES IN (14C)GLYCINE-INCORPORATING ACTIVITIES OF RAT-ADRENAL MICROSOMES AND SOLUBLE CELL FRACTION DURING PROLONGED ADRENOCORTICOTROPIN ADMINISTRATION. , 1964, Biochimica et biophysica acta.

[5]  R. Farese.  INHIBITION OF THE STEROIDOGENIC EFFECT OF ACTH AND INCORPORATION OF AMINO ACID INTO RAT ADRENAL PROTEIN IN VITRO BY CHLORAMPHENICOL. , 1964, Biochimica et biophysica acta.

[6]  E. D. Bransome,et al.  INCORPORATION OF AMINO ACIDS INTO RAT ADRENAL PROTEIN IN VIVO: EFFECTS OF ADRENOCORTICOTROPHIN AND GROWTH HORMONE. , 1963, Endocrinology.

[7]  Robert V Farese,et al.  Effect of Adrenocorticotrophin on Adrenal Protein Synthesis1 , 1963 .

[8]  B. Sacktor,et al.  INHIBITION OF THE SYNTHESIS OF PROTEIN IN INTACT ANIMALS BY ACETOXYCYCLOHEXIMIDE AND A METABOLIC DERANGEMENT CONCOMITANT WITH THIS BLOCKADE. , 1963, Biochemical pharmacology.

[9]  J. Ferguson,et al.  PROTEIN SYNTHESIS AND ADRENOCORTICOTROPIN RESPONSIVENESS. , 1963, The Journal of biological chemistry.

[10]  G. Constantopoulos,et al.  Cleavage of cholesterol side chain by adrenal cortex. I. Cofactor requirement and product of clevage. , 1961, The Journal of biological chemistry.

[11]  R. Busch,et al.  Practical procedure for estimation of corticosterone or hydrocortisone. , 1958, Clinical chemistry.

[12]  A. Schally,et al.  In vitro bioassay of corticotropin: modification and statistical treatment. , 1955, Endocrinology.

[13]  G. W. Thorn,et al.  Use of ACTH in the diagnosis of adrenal cortical insufficiency. , 1955, The American journal of medicine.

[14]  D. Stone,et al.  Studies on ACTH action in perfused bovine adrenals: the site of action of ACTH in corticosteroidogenesis. , 1954, Archives of biochemistry and biophysics.

[15]  S DeCandia,et al.  [Cushing's syndrome]. , 1951, Il Policlinico. Sezione pratica.