Intensive venous sampling of adrenocorticotropic hormone in rats with sham or paraventricular nucleus lesions

Abstract

Adrenocorticotropic hormone (ACTH) secretion from the anterior pituitary is predominantly regulated by corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) synthesized in neurons of the paraventricular nucleus (PVN) of the hypothalamus. Secretion of ACTH occurs in pulsatile bursts. To explore the relationship between hypothalamic control and the pulsatile pattern of ACTH secretion, we measured ACTH in 2 min blood samples over 4 h in rats with intact and lesioned PVN during hypovolemic-stress or control conditions and also measured median eminence (ME) levels of CRH, AVP, and oxytocin (OT). Mean plasma ACTH was highest in the sham lesioned-hypovolemic group, lowest in the sham lesioned-control group and intermediate in the two PVN-lesioned groups. CRH in the ME was negligible in the lesioned animals and correlated with OT and AVP. Pulsatile secretion was observed despite PVN ablation. Visual inspection of composite time series suggested different temporal patterns of ACTH secretion. Principal components analysis of the individual ACTH time series revealed three significant eigenvectors which correlated differentially with the three treatment groups. Neither lesioned group had the steep rise over 10 min seen in plasma ACTH in the non-lesioned groups. Delayed ACTH rise after 30-60 min occurred in all but the sham control group. Our data suggest that CRH is responsible for immediate secretion of ACTH in response to hypovolemic stress and that regulators from non-PVN sites may be responsible for more delayed secretion of ACTH in this setting. The persistence of ME AVP and OT levels in the face of > 90% reduction in ME CRH levels leaves open the question of a role for one or both of these peptides in the delayed ACTH response following stress onset and in the generation of pulsatile ACTH secretory bursts.

Role of hypothalamic inputs in maintaining pituitary-adrenal responsiveness in repeated restraint

“…After PVH lesion, the plasma ACTH response to short and relatively weak neurogenic stressors may be completely blocked, but most, if not all, medium-to-strong, acute, stressful stimuli will elicit an almost normal ACTH and corticosterone response (7,8,10,27,29,40). The present findings are in agreement with these data.…”

“…2). Various stress paradigms act through different pathways, because in some cases the elimination of PVH abolished acute stress-induced ACTH elevation [hemorrhage (10), early response after bacterial lipopolysaccharide (13), elevated platform stress (28)], but with some other stressors, considerable ACTH and/or corticosterone elevation occurs even after lesioning the PVH [hypovolemia (7), ether (8,27,29), immobilization, electrical stimulation of the skin (14), footshock, IL-1␤ (40)]. …”

Gonadectomy Reverses The Sexually Diergic Patterns Of Circadian and Stress‐Induced Hypothalamic‐Pituitary‐Adrenal Axis Activity In Male and Female Rats

“…In the present study, we were unable to determine pulses in ACTH due to limitations of the frequency of sampling and the prolonged sampling period. However, ACTH release is known to occur in a pulsatile manner in the rat (34)(35)(36). There is evidence of an intrinsic rhythmicity of ACTH release from pituitary corticotrophs in humans (37), but it is likely that these pulses are in turn generated from the hypothalamus in the rat (35,38).…”

The Role of Oxytocin in Neuropsychiatric Disorders

“…In rats, OT has been demonstrated to potentiate the release of ACTH induced by CRH: in fact, if CRH is responsible for the immediate secretion of ACTH following an acute stress, when CRH levels begin to decrease during prolonged stress, the persistent level of OT in the median eminence seems to be related to the delayed ACTH response and the generation of ACTH pulsatile secretory bursts [13]. On the contrary, in humans, OT infusion inhibited the plasma ACTH responses to CRH, and suckling and breast stimulation increased and decreased, respectively, plasma OT and ACTH levels; these evidences would indicate an inhibitory influence of OT on ACTH secretion.…”