Discordance of plasma DHEA-S, DHEA, and cortisol responses with various ACTH regimens

Abstract

The origin and time course of ACTH-stimulated adrenal androgens are controversial. Since previous protocols have used differing ACTH preparations and routes of administration, we sought to compare plasma DHEA and DHEA-S responses to four ACTH regimens. Fourteen young men underwent the following five three-day study periods: (1) placebo, (2) α 1–24 ACTH, 400 μg intravenously (IV); (3) α1–39 ACTH, 400 μg intramuscularly (IM); (4) α1–18 (D-Ser 1, Lys 17, Lys 18) ACTH, 400 μg IM; and (5) α1–18 ACTH, 400 μg IV. α1–18 ACTH IV had the most potent and prolonged corticotropic effect, listing more than 24 hours, as measured by plasma cortisol, 17-OHCS, and cortisol secretion rates. α1–39 ACTH and α1–18 ACTH IM were corticotropic up to 12 hours, and α1–24 ACTH IV was corticotropic only up to one hour. Plasma DHEA rose acutely at one hour with all of the ACTH regimens ( P < 0.05). This response was correlated with cortisol ( r = 0.62, P < 0.01) and reflected the relative corticotropic potency of each of the ACTH regimens. Plasma DHEA-S, on the other hand, did not rise acutely at one hour with any of the regimens. DHEA-S did rise at 12 hours with three of the ACTH regimens (α-1–24, α1–39, α1–18 IM), but this response was not synchronous with cortisol ( r = 0.14, P = NS). The discordance in DHEA-S to DHEA and cortisol responses suggest that ACTH induction of DHEA sulfurylation is a delayed step, possibly occurring in extraadrenal tissues. These results also demonstrate that the synthetic ACTH analogue, α1–18 ACTH is a potent adrenal androgen secretogogue.