Characteristics of corticosteroid inhibition of adrenocorticotrophin release from the anterior pituitary gland of the rat

Abstract

The occurrence and nature of corticosteroid inhibition of ACTH secretion at the rat anterior pituitary gland was investigated using three experimental models: animals bearing lesions of the basal hypothalamus, and two preparations of the gland incubated in vitro; these were tissue segments and collagenase-dispersed cells. Release of ACTH in the experiments was provoked using one of three distinct stimuli: acid extracts of whole hypothalami, corticotrophin releasing activity released by serotonin from hypothalami incubated in vitro and synthetic ovine corticotrophin releasing factor. Irrespective of whether ACTH was measured directly by radioimmunoassay (in the experiments in vitro) or indirectly in terms of corticosterone production (in the lesioned animals), its stimulated release from the anterior pituitary gland was inhibited by corticosterone. Two phases of inhibition were observed; these had some of the characteristics inferred previously from experiments with intact animals and designated fast feedback and delayed feedback. However, the fast feedback demonstrable in lesioned animals did not show the rate-sensitivity shown previously in intact animals. 11-Deoxycortisol (or 11-deoxycorticosterone) and prednisolone proved to be agonists of corticosterone in provoking fast feedback in lesioned animals, whereas they had been shown respectively to act as an antagonist or to have no effect in intact rats. Several steroids were able to cause delayed feedback in lesioned rats, but beclomethasone dipropionate (shown to be an agonist of corticosterone in intact rats) proved to have no inhibitory effect at the anterior pituitary gland of lesioned animals. It is concluded that the dynamics of corticosteroid feedback mechanisms at the anterior pituitary gland, as indicated by experiments in lesioned animals, differ from those operative in the intact animals. Other work suggests that a more important site for such inhibitory mechanisms in vivo is the hypothalamus.

The Combination of 17α-Hydroxyprogesterone and 11-Epicortisol Prevents the Delayed Feedback Effect of Natural and Synthetic Glucocorticoids

“…As far as the anterior pituitary gland is concerned, 17a-OH-progesterone has no antagonistic effect on the early delayed feedback action of corticosteroids on the re sponse of mediobasal hypothalamic-lesioned rats to injec tion of hypothalamic extract [19]. The present results also show that the combination of the two steroids is ineffective in counteracting the inhibitory effects of corticosterone on subsequent in vitro responsiveness to AVP or CRF-4I at the anterior pituitary level.…”

“…The fact that the combination of these antagonists effectively block the early delayed effects of a variety of feedback agonists in vivo implies that inhibition of ACTH secretion from the pituitary gland can be over-ridden by an increase in CRF-AVP drive from the hypothalamus. We have previ ously shown that feedback at the pituitary level can be over come by increasing the ACTH-releasing stimulus [19]. Therefore the sites of action of the antagonistic steroids must be located either in the hypothalamus or at extrahypothalamic sites.…”

Differential Impact of Audiogenic Stressors on Lewis and Fischer Rats: Behavioral, Neurochemical, and Endocrine Variations

“…Consistent with elevated circulating corticosterone levels following noise exposure, marked strain differences were evident with respect to interstitial levels of corticosterone at the anterior pituitary, with noise exposure markedly elevating corticosterone availability in the Fischer, but not in the Lewis rats. Corticosterone-induced suppression of the HPA axis occurs both at pituitary and suprapituitary levels (Mahmoud et al, 1984;Widmaier and Dallman, 1984). The finding that male Fischer and Lewis rats display similar sensitivity to peripherally administered dexamethasone (Gomez et al, 1998) suggests similar glucocorticoid receptor function between these strains.…”

60 YEARS OF NEUROENDOCRINOLOGY: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies

“…This time delay of a few minutes is presumably due to the time needed by the adrenal for de novo synthesis CORT in response to ACTH, since in contrast to peptides hormones (e.g., CRH and ACTH), CORT cannot be pre-synthesized and stored within adrenal steroidogenic cells due to its lipophilic nature. Once released into the general circulation, CORT activates a fast (presumably non-genomic) negative feedback mechanism at the level of the pituitary that still remains to be fully characterized (Jones et al 1972, 1974, Rotsztejn et al 1975a,b, Mahmoud et al 1984, Widmaier & Dallman 1984, Hinz & Hirschelmann 2000, Russell et al 2010.…”