Effects of Corticosteroids on Hypothalamic Corticotropin Releasing Factor and Pituitary ACTH Content

The possible binding of ³H-dexamethasone (Dx)to the anterior pituitary and the effect of the steroid on neo-synthesis and release of ACTH of glands incubated with crude CRF extracts were examined. Neosynthesis of ACTH was determined by immunoprecipitation after incorporation of ¹⁴C-phenylalanine into the peptide. Using a cell-free system, ³H-Dx was shown to combine with the nuclear fraction of the pituitary. Short-term in vitro pre-treatment with Dx suppressed the CRF-induced hormonal release, but did not alter ACTH biosynthesis. The releasing mechanism, on the other hand, did not appear to be related to de novo synthesis. Prolonged in vivo administration of high concentrations of Dx initially caused a decrease of ACTH synthesis and, later, also impaired the synthesis of total proteins. Synthesis and release of ACTH may be dissociated, but there is a possibility that a correlation exists between these two processes. On the other hand and as far as the direct effect of Dx on the pituitary is concerned, the nuclear uptake of the steroid probably reflects an early step in the modulation of corticotropic activity.

Section: Discussionmentioning

confidence: 94%

Pituitary Nuclear Retention of Dexamethasone and ACTH Biosynthesis

Koch¹,

Bucher²,

Mialhe³

1974

“…This suggests that the mode of action of IM is qualitatively differnt from that of conventional stressors, which are considered to cause an immediate increase in the secretion of CRF from the medi an eminence [4,6], an effect which is overcome by cortico steroids [1,4].…”

Section: Discussionmentioning

confidence: 99%

ACTH and Corticosterone Secretion Following Indomethacin, in Intact, Adrenalectomized and Dexamethasone-Pretreated Male Rats

Weidenfeld¹,

Siegel²,

Conforti³

et al. 1983

The present study was designed to determine the role of glucocorticoids in the mediation of the stimulatory effect of indomethacin (IM) on the hypothalamo-hypophyseal-adrenal axis. Intact male rats were treated with a single injection of either dexamethasone (Dex; 20 µg/100 g body weight), IM (5 mg/100 g body weight), or IM + Dex or their respective vehicles. In Dex-treated rats, ACTH and corticosterone (CS) were significantly reduced over a period of 20 h as compared to the vehicle-treated group. As we have previously demonstrated, injection of IM markedly elevated serum ACTH and CS for at least 20 h. Administration of Dex 2 h prior to IM treatment delayed the stimulatory effect of IM for 5 h; subsequently, however, Dex was without effect. In adrenalectomized rats, ether stress elicited a marked rise in serum ACTH levels. On the contrary, IM was completely ineffective in these rats. These studies suggest that the mode of action of IM in causing hypersecretion of ACTH and CS is by interfering with the negative feedback effects of the glucocorticoids.

“…We [21] also reported that the intraperitoneal administration of dexamethasone resulted in a decrease in hypothalamic CRF content in rats. Chowers et al [2] showed that the dexameth asone implants in the ME significantly reduced the ACTH content of the anterior pituitary, hypothalamic CRF, and adrenal weight. Corbin et al [3] also demonstrated that dex amethasone placement in the ME reduced plasma and adre nal corticosterone levels and adrenal weight.…”

Section: Discussionmentioning

confidence: 99%

The Site of Inhibitory Action of a Natural (Corticosterone) and Synthetic Steroid (Dexamethasone) in the Hypothalamus-Pituitary-Adrenal Axis

Sakakura¹,

Yoshioka²,

Kobayashi³

et al. 1981

Only a few reports have appeared which have attempted to determine whether the naturally occurring steroid, corticosterone, has the same site of action in the hypothalamus-pituitary-adrenal axis as the synthetic steroid, dexamethasone. The present studies help to define the site of inhibition of both corticosterone and dexamethasone on the hypothalamus-pituitary-adrenal axis. Infusion of 20 or 202 µg corticosterone over 6 h significantly reduced hypothalamic CRF (corticotropin-releasing factor) content, whereas it did not reduce plasma ACTH levels in normal rats. This finding indicates the possibility that the infusion of corticosterone may decrease the hypothalamic CRF content by reducing CRF production or enhancing intracel-lular and/or extracellular CRF degradation. On the other hand, infusion of 20 µg dexamethasone for 6 h to normal rats significantly decreased plasma ACTH levels, but did not alter the hypothalamic CRF content. This finding indicates that dexamethasone may inhibit the release or/and production of ACTH in the anterior pituitary. In addition, relatively large doses of corticosterone (504 µg/rat) and dexamethasone (202 µg/rat) may suppress CRF content and ACTH release at the level of both the hypothalamus and anterior pituitary.