The rapid release of corticosterone from the adrenal induced by ACTH is mediated by nitric oxide acting by prostaglandin E2.
The adrenal cortex is a major stress organ in mammals that reacts rapidly to a multitude of external and internal stressors. Adrenocorticotropin (ACTH) is the main stimulator of the adrenal cortex, activating corticosteroid synthesis and secretion. We evaluated the mechanism of action of ACTH on adrenals of male rats, preserving the architecture of the gland in vitro. We demonstrated that both sodium nitroprusside (NP), a nitric oxide (NO) donor, and ACTH stimulate corticosterone release. NO mediated the acute response to ACTH because Nomega-nitro-l-arginine methyl ester, a NO synthase inhibitor, and hemoglobin, a NO scavenger, blocked the stimulation of corticosterone release induced by ACTH. NP stimulated prostaglandin E release, which in turn stimulated corticosterone release from the adrenal. Additionally, indomethacin, which inhibits cyclooxygenase, and thereby, prostaglandin release, prevented corticosterone release from the adrenal induced by both NP and ACTH, demonstrating that prostaglandins mediate acute corticosterone release. Corticosterone content in adrenals after incubation with ACTH or NP was lower than in control glands, indicating that any de novo synthesis of corticosterone during this period was not sufficient to keep up with the release of the stored hormone. The release induced by ACTH or NP depleted the corticosterone content in the adrenal by approximately 40% compared with the content of glands incubated in buffer. The mechanism of rapid release is as follows: NO produced by NO synthase activation by ACTH activates cyclooxygenase, which generates PGE(2), which in turn releases corticosterone stored in microvesicles and other organelles.
Mohn
Claudia E
CE
Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, Serrano 669, 1414 Buenos Aires, Argentina.
Fernandez-Solari
Javier
J
De Laurentiis
Andrea
A
Prestifilippo
Juan Pablo
JP
de la Cal
Carolina
C
Funk
Richard
R
Bornstein
Stefan R
SR
McCann
Samuel M
SM
Rettori
Valeria
V
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D009599:Nitroprusside; D009569:Nitric Oxide; D000324:Adrenocorticotropic Hormone; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester; D003345:Corticosterone