Further Evidence for a Central Stimulatory Action of Catecholamines on Adrenocorticotropin Release in the Rat

Abstract

Catecholamines may stimulate ACTH secretion during stress. To investigate the nature and site of such an action, plasma ACTH was measured in four groups of unanesthetized adult female rats with an indwelling carotid cannula. Sequential 300-microliter blood samples were taken 60 min, 30 min, and immediately before an intracerebroventricular (icv) infusion of 2.5 microliter adrenaline or noradrenaline and 5, 15, 45, 60, and 120 min after the infusion. The four groups were: 1) intact rats; 2) rats infused 7 days after undergoing a discrete bilateral lesion of the ventral noradrenergic ascending bundle caused by 6-hydroxydopamine, which depleted their hypothalamic adrenaline and noradrenaline levels by 90% and 80%, respectively; 3) rats infused 30 min after pretreatment via the icv route with either prazosin or propranolol; and 4) rats infused 16 and 2 h after two successive intracarotid injections of an anti-rCRH-41 serum. In another group, the effects of icv catecholamine administration were compared with those of an intracerebral (ic) microinfusion close to a single paraventricular nucleus (PVN). Finally, in two additional groups blood was sampled at the above-mentioned times before and after a 2-min ether inhalation by intact rats or prazosin- and/or propranolol-pretreated rats. In the intact rats (group 1), a stress-like stimulatory dose response was noted after both adrenaline and noradrenaline infusions, with a half-maximal effect at concentrations of about 0.6 nmol and a maximal effect at 2.7 nmol or more. At maximally effective doses, adrenaline was significantly more active than noradrenaline. In the rats with ventral noradrenergic ascending bundle lesions (group 2), 2.7 nM adrenaline or noradrenaline stimulated ACTH release as in the controls without lesions. In group 3, prazosin blocked the ACTH responses to both adrenaline and noradrenaline, whereas propranolol only blocked the response to adrenaline. In group 4, i.e. rats pretreated with an anti-rCRH-41 serum, the amplitude of the ACTH surge after icv adrenaline or noradrenaline infusion was halved. A unilateral ic catecholamine microinfusion next to the PVN (half the icv dose given in group 1) led to a rapid ACTH release that peaked at half the response measured in the icv infused rats. Ether stress-induced ACTH release was decreased by 50-60% after icv pretreatment with 1 or 10 micrograms prazosin, 1 or 6.5 micrograms propranolol, or a combined dose comprising 1 microgram of both. The following conclusions were reached.(ABSTRACT TRUNCATED AT 400 WORDS)

Catecholaminergic Control of Mitogen-Activated Protein Kinase Signaling in Paraventricular Neuroendocrine NeuronsIn VivoandIn Vitro: A Proposed Role during Glycemic Challenges

“…First, our NE injections elevated circulating ACTH/corticosterone, confirming many reports (Szafarczyk et al, 1987;Leibowitz et al, 1988Leibowitz et al, , 1989Saphier and Feldman, 1989;Itoi et al, 1994Itoi et al, , 1999Helmreich et al, 2001;Cole and Sawchenko, 2002). Second, corticosterone elevations reportedly occur only from PVH-injected NE [with a small effect in dorsomedial hypothalamus (DMH)] and not from NE injected into surrounding areas (Leibowitz et al, 1989).…”

Systemic administration of leptin decreases plasma corticosterone levels: Role of hypothalamic norepinephrine

“…Regulation of the HPA axis is under the control of corticotrophin releasing hormone (CRH) neurons. These neurons are found in a number of areas in the brain including the hypothalamus (Chrousos, 1992;Nemeroff, 1992;Szafarczyk et al, 1987). In the hypothalamus, the paraventricular nucleus (PVN) contains a high concentration of CRH cell bodies.…”

“…In the hypothalamus, the paraventricular nucleus (PVN) contains a high concentration of CRH cell bodies. When stimulated, these neurons secrete CRH, which in turn causes the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary (Chrousos, 1992;Nemeroff, 1992;Szafarczyk et al, 1987). This then, acts on the adrenal cortex to cause an increase in corticosterone (CS) completing the activation of the stress axis.…”

“…This then, acts on the adrenal cortex to cause an increase in corticosterone (CS) completing the activation of the stress axis. Norepinephrine (NE) plays a critical role in stimulating CRH secretion (Plotsky et al, 1989;Szafarczyk et al, 1987). The PVN receives rich noradrenergic innervation from brainstem noradrenergic nuclei and their terminals are known to synapse with CRH cell bodies in the PVN (Szafarczyk et al, 1987).…”

Glucocorticoids Provoke a Shift from α2‐ to α1‐Adrenoreceptor Activities in Cultured Hypothalamic Slices Leading to Opposite Noradrenaline Effect on Corticotropin‐Releasing Hormone Release

“…In fact, the CRH-synthesizing neurons in the parvocellular portion of the paraventricular nucleus (PVN) of the hypothalamus receive direct catecholaminergic innervation originating from the lower brainstem and conveyed by the ventral noradrenergic ascending bundle (VNAB) Lipositz et al, 1986). As demonstrated in various in vivo and in vitro approaches, a stimulatory effect predominates in the central catecholaminergic control of the CRH-ACTH axis, particularly on basal and stressinduced CRH secretion at the hypothalamic level (Axelrod and Reisine, 1984;Ganong, 1984;Guillaume et al, 1987;Plotsky, 1987;Szafarczyk et al, 1987Szafarczyk et al, , 1995Tsagarakis et al, 1988;Widmaier et al, 1989).…”