Regulation of Adrenal Ornithine Decarboxylase by Adrenocorticotropic Hormone and Cyclic AMP

Abstract

A B S T R A C T Adrenal ornithiine decarboxylase activity was stimulated in a dose-related manner after administration of ACTH or dibutyryl (6N-2'-O-dibutyryl) cyclic AMP to hypophysectomized rats. Little effect was observed for 2 h, but striking increases in enzyme activity were observed 4 h after administration of these substances. Effects of ACTH and dibutyryl cyclic AMP were not secondary to stimulation of steroidogenesis, since hydrocortisone had no effect on adrenal ornithine decarboxylase although it did stimulate activity of the enzyme in the liver and kidney.ACTH, given subcutaneously to hypophysectomized rats, induced striking increases in adrenal cyclic AMP levels within 15-30 min with a fall towards the base line in 1 h. Increases in ornithine decarboxylase activity lag several hours after this endogenous cyclic AMP peak, in contrast to the stimulation of steroidogenesis by the nucleotide that requires only 2-3 min. After graded doses of ACTH, increases in adrenal cyclic AMP levels at 30 min were paralleled by proportional increases in adrenal ornithine decarboxylase activity 4 h after hormone treatment. Whereas maximal levels of adrenal steroidogenesis have been observed at tissue cyclic AMP levels of 6 nmol/g, ACTH is capable of inducing increases in nucleotide levels up to 200 nmol/g or more. These high tissue levels of cyclic AMP, although unnecessary for maximal steroidogenesis, appear to stimulate adrenal ornithine decarboxylase activity.Several results in addition to the time lag in the stimulation of ornithine decarboxylase activity suggest a mechanism involving accumulation of the enzyme or some factor needed for its activity rather than direct activation of the enzyme by cyclic AMP. Thus, the addition of cyclic AMP directly to the ornithine decarboxylase assay mixture in vitro was without stimulatory Receiz'ed for publication 5 May 1972 and in revised form 27 March 1973. effect. In addition, actinomycin D or cycloheximide in doses sufficient to block adrenal RNA and protein synthesis, respectively inhibited the stimulation of ornithine decarboxylase activity by ACTH in vivo. An adrenocortical cancer was found to maintain ornithine decarboxylase activity at very high levels, but did so at much lower cyclic AMP levels than those of ACTH-stimulated adrenals.It is concluded that ACTH stimulates adrenal ornithine decarboxylase activity and that this effect may be mediated by cyclic AMP. However, cyclic AMP does not appear to be a determinant of the high level of enzyme activity found in adrenocortical cancer.

The variations of estrogen receptor, progesterone receptor, cAMP, ODC activity and RNA synthesis of deciduomata in pseudopregnant rats.

“…The ornithine decarboxylase (ODC) activity of the prostate is stimulated by testosterone (Pegg et al 1970), that of the rat uterus or chick oviduct is stimulated by estradiol (Cohen et al 1970; Kaye et al 1971;Villee and Loring 1975), that of the liver is stimulated by growth hormone (Janne and Raina 1969), and that of the adrenal is stimulated by adrenocorticotropic hormone (Richman et al 1973). Ovarian ODC activity rises sharply during the pre-ovulatory surge of luteinizing hormone (Kobayashi et al 1971), and the rise of activity can be prevented by the injection of anti-LIT before proestrus.…”

Regulation of ornithine decarboxylase activity by corticotropin in adrenocortical tumor cell clones: roles of cyclic AMP and cyclic AMP-dependent protein kinase.

“…This response is of particular interest because the enzyme is rate-limiting in the synthesis of polyamines (10), which are implicated in the control of tissue growth (11)(12)(13). Because accumulation of cyclic AMP temporally precedes changes in ornithine decarboxylase activity and cyclic AMP analogues reproduce the hormonal effect, a cyclic AMP-dependent mechanism has been postulated for hormonal regulation of ornithine decarboxylase activity (1)(2)(3)(4)(5). Furthermore, cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) has been implicated in the stimulation of ornithine decarboxylase by trophic hormones (14).…”

“…In another series of mutant subclones, Yl(Kin), cyclic AMP-dependent protein kinase activity in cytosol fractions 1 …”

Cell cycle specific fluctuations in adenosine 3':5'-cyclic monophosphate and polyamines of Chinese hamster cells.

“…Recent studies have shown that dibutyryl-adenosine 3': 5'-cyclic monophosphate can induce ornithine decarboxylase activity in the adrenal medulla and in numerous rat tissues (19)(20)(21)(22)(23). Further, it has been shown that cold exposure which leads to cholinergic stimulation of the adrenal medulla of the rat results in a marked increase in adenosine 3': 5'-cyclic monophosphate (cAMP) levels, followed by a rapid increase in ornithine decarboxylase activity (24,25).…”