Low sodium intake enhances sensitivity of 11-deoxycortisol and deoxycorticosterone to ACTH in ACTH-suppressed normal subjects.
Continued administration of ACTH to patients with hypopituitarism produced normal increases in steroids dependent on microsomal cytochrome P450(21) and P450(17 alpha) but reduced responses of steroids dependent on mitochondrial cytochrome P450(11 beta-18). To explore possible mechanisms and to determine whether this dissociation occurs with short-term ACTH suppression, we have examined the steroid responses to ACTH after 1 h in 12 normal subjects after equilibration on sodium intakes of 124 mmol/d [normal sodium diet (NSD)], 22 mmol/d [low sodium diet (LSD)], and 240 mmol/d [high sodium diet (HSD)] before and during continued ACTH suppression with dexamethasone (DEX). Two distinct patterns of steroid responses were observed. Deoxycorticosterone (DOC) responses were initially reduced during LSD-DEX but eventually returned to the NSD-control (NSD-CONT) values; in contrast 18-hydroxydeoxycorticosterone and corticosterone remained suppressed. 11-Deoxycortisol and 21-deoxycortisol showed patterns similar to DOC, with a return to normal ACTH responses on LSD-DEX. Basal cortisol levels were reduced and the ACTH response was unchanged by LSD. HSD-DEX reduced basal levels of all steroids as well as their ACTH responses. LSD and/or increased activity of the renin-angiotensin system have a significant impact on 17 alpha- and 21-hydroxylation functions in the zona fasciculata to maintain a normal ACTH response of microsomally dependent steroids under these conditions. In contrast, on HSD-DEX with the renin-angiotensin system suppressed, there is generalized impairment of steroid responses to ACTH.
Kater
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San Francisco General Hospital Medical Center, CA 94110.
Biglieri
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EG
Irony
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D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D003345:Corticosterone / Q000097:blood; D003350:Cortodoxone / Q000494:pharmacology*; D003900:Desoxycorticosterone / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000378:metabolism; D012083:Renin / Q000097:blood; D012964:Sodium / Q000008:administration & dosage / Q000494:pharmacology*; D013256:Steroids / Q000097:blood* / Q000378:metabolism; D015383:Zona Fasciculata / Q000737:chemistry
D013256:Steroids; D003900:Desoxycorticosterone; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D012964:Sodium; D012083:Renin; D011188:Potassium; D003345:Corticosterone; D003350:Cortodoxone; D006854:Hydrocortisone