Increased Responsivity of Adrenals from Reserpine-Treated or Stressed Rats to Steroidogenic Activity of AGTH

Abstract

In an attempt to determine whether cate-cholamines serve a permissive role for the steroidogenic action of adrenocorticotrophic hormone (ACTH) in the adrenal cortex, as has been reported for the lipolytic action of ACTH on the fat pad(l), adrenals from re-serpine-treated rats were compared to glands from untreated rats with respect to their re-sponsivity in vitro to steroidogenic agents. No evidence for a permissive role for catechola-mines was obtained in the adrenal system, even when glands from resperine-treated rats were preincubated with acetylcholine and re-serpine in an attempt further to deplete residual catecholamines from the adrenals(2).

However, an interesting difference in response to in vitro stimulation by ACTH, cyclic 3′,5′-adenosine monophosphate (3′,5′-AMP) or reduced triphosphopyridine nucleo-tide (NADPH) was shown by adrenals from reserpine-treated rats compared to those from untreated rats. The adrenals of the former group showed a considerably greater production of corticosteroids than those from untreated animals, in response to ACTH or cyclic adenosine 3‘,5‘-monophosphate (3′,5′-AMP), without change in the steroidogenic response to reduced triphosphopyridine nu-cleotide (NADPH). This reserpine effect appears to result from non-specific stress activation of adrenals in vivo, since injections of formaldehyde or exogenous ACTH reproduced the pattern of in vitro response observed following reserpine administration. The results of these investigations are presented here and discussed in connection with current concepts of the mechanism of action of ACTH on the adrenal cortex.

Experimental. Male Sprague-Dawley rats (135-150 g) were used throughout. Groups of animals were treated with one of the following regimens: Reserpine (Serpasil, Ciba): administered in 2 daily injections for 2 days, 0.1 ml (0.25) mg, intraperitoneally on the first day and 0.05 ml (0.125 mg) intramuscularly on the second day.

When used in vitro, reserpine (Mann Research Lab., Inc., New York) was added to the incubation medium as a suspension in KRB to give a final concentration of 1 mg/ ml.