Adrenocorticotropic hormone elevates gene expression for catecholamine biosynthesis in rat superior cervical ganglia and locus coeruleus by an adrenal independent mechanism

Abstract

Classically, upon hypothalamic stimulation, adrenocorticotropic hormone (ACTH) is released from the pituitary and acts on melanocortin 2 receptors (MC2R) in the adrenal cortex, stimulating glucocorticoid synthesis and release. Our earlier studies suggested that ACTH might have a direct effect on sympathetic ganglia. To analyze further the involvement of ACTH in regulation of gene expression of norepinephrine (NE) biosynthetic enzymes, we examined the effect of bilateral adrenalectomy (ADX) of Sprague-Dawley male rats. Fourteen days post-ADX, as expected, plasma ACTH was elevated, and levels of tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH) and MC2R mRNAs in superior cervical ganglia (SCG), and TH mRNA in locus coeruleus (LC) were increased compared with sham-operated animals. To determine effect of pulsatile elevation of ACTH, corticosterone pellets were implanted to ADX rats. Similar to immobilization (IMO) stress ACTH injections to these animals caused a rise in ACTH in plasma and triggered elevation of TH and DBH mRNAs in SCG and in LC with single and repeated daily injections, and MC2R mRNA in SCG with single injections. To study the effect of ACTH in isolated cells, primary cultures of rat SCG were transfected with TH and DBH promoter constructs and treated with ACTH. In agreement with the in vivo data, ACTH elevated their promoter activities similar to levels triggered by cyclic AMP analog. ACTH in the human SK-N-SH neuroblastoma cells increased TH and DBH promoter activity and endogenous DBH mRNA levels. The results show that ACTH can have a direct effect on transcription and gene expression of NE biosynthetic enzymes even without contribution of adrenal hormones.

Effect of chronic intermittent hypoxia on noradrenergic activation of hypoglossal motoneurons

“…Stress is among the factors that may link CIH to increased noradrenergic transmission to XII motoneurons through its actions on noradrenergic cells mediated by the adrenocorticotropic hormone and glucocorticoids. For example, stress and elevated glucocorticoid levels increase expression of tyrosine hydroxylase and dopamine ␤-hydroxylase, two key enzymes in the synthesis of norepinephrine (9,37,50). However, whether and when CIH of moderate severity, such as that used in our study, is associated with stress and increased glucocorticoid levels is not clear.…”

Dual Effect of Catecholamines and Corticosterone Crosstalk on Pineal Gland Melatonin Synthesis

“…The hormonal production induced by the electrical field stimulation of the sympathetic nerve terminals of the pineal gland is completely abolished by β-adrenergic blockers [33], with α 1 -adrenoceptor activation seeming to have a relatively small effect on pineal melatonin production in vivo [37,38,39]. Defense responses increase circulating [35] and cervical superior ganglia (which innervates the pineal gland) release of catecholamines [34], leading to maximal adrenergic (β+α 1 ) pineal stimulation. The present work shows that pineal glands incubated with β+α 1 -adrenergic agonists produce increased levels of NAS and melatonin, confirming the in vitro observation of α 1 -adrenoceptor-dependent enhancement of pineal hormonal synthesis [36].…”

“…In the context of the immune-pineal axis [50], the present data show that corticosterone released at the beginning of a defense response [51] would act on the pineal gland concurrent with high sympathetic input [34], resulting in suppression of nocturnal melatonin synthesis, which is essential for a number of immune processes, including leukocyte migration [15,17,45]. As the innate immune response progresses, the adrenergic tone decreases whilst the release of adrenal cortical hormones is maintained during the recovery phase.…”

“…Stressful conditions enhance the sympathetic tonus, leading to increased neurotransmitters released in the pineal gland [34] and increased levels of circulating catecholamines [35]. In such conditions, it is plausible to expect that a heightened adrenergic stimulation occurs in pinealocytes, with adrenoceptor subtypes α 1 and β being concomitantly stimulated.…”

Efeito da melatonina sobre a viabilidade de células granulares de cerebelo em cultura depende do contexto celular

“…O AMPc, por sua vez, ativa a proteína quinase A II dependente de AMPc (PKAII) (Simonneax e Ribelaga, 2003). O aumento da atividade simpática pode elevar as concentrações disponíveis de NA na fenda sináptica ativando adrenoceptores α1 (Sabban et al, 2004;Serova et al, 2008) que potencia em até vinte vezes a síntese de melatonina induzida pela ativação de adrenoceptores β1 (Chik e Ho, 1989). Os adrenoceptores α1 ativam fosfoquinase C (PKC) através da mobilização de cálcio por inositol trifosfato (IP3).…”