Encyclopedia of Animal Cognition and Behavior

Living Edition
| Editors: Jennifer Vonk, Todd Shackelford


  • Reema ChaudharyEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-47829-6_1439-1



Adrenalin is a hormone and neurotransmitter which is secreted by the adrenal glands and certain neurons in response to panic, threat, or fear (fight or flight response). Stress is another stimulus for secretion of this hormone.

Adrenal Glands

The paired glands located superior to each kidney in the retroperitoneal space are called adrenal (suprarenal) glands. The adrenal glands divided into two structurally and functionally distinct regions which are as follows:
  • Adrenal cortex, which comprises 89–90% of the gland and located peripherally.

  • Adrenal medulla, which is small and centrally located.

A connective tissue capsule covers the gland. The adrenal glands are richly supplied with the blood flow. Steroid hormones are produced by the adrenal cortex which is essential for maintaining electrolyte balance in the body. Complete loss of adrenocortical hormones lead to death due to dehydration and electrolyte imbalance in a few days to week which can be treated only by hormonal therapy. The adrenal medulla produces three catecholamine hormones – norepinephrine (noradrenaline), epinephrine (adrenalin), and a small amount of dopamine.

Adrenal Cortex

The adrenal cortex is subdivided into three zones which are as follows:
  • Zona glomerulosa: This outer zone lies deep to the connective tissue capsule and composed of cells which are closely packed and arranged in spherical clusters. These cells secrete hormones called mineralocorticoids because they affect mineral homeostasis.

  • Zona fasciculata: It is the middle zone and widest of the three zones and consists of cells arranged in long and straight columns. Glucocorticoids are mainly secreted by these cells and maintain glucose homeostasis.

  • Zona reticularis: This is the inner zone and consists of cells which are arranged in branching cords and synthesize small amounts of weak androgens having masculinizing effects.

Adrenal Medulla

This is the inner part of the adrenal gland which is a modified sympathetic ganglion of the autonomic nervous system (ANS). It develops from the same embryonic tissue as all other sympathetic ganglia, but its cells lack axons. The cells of the adrenal medulla which secrete hormones are called as chromaffin cells.

The two major hormones synthesized by the adrenal medulla are epinephrine and norepinephrine (NE), also called as adrenaline and noradrenaline, respectively.

Physiological Effects

It acts by binding to different adrenergic receptors (α1, α2, β1, β2, and β3) of the sympathetic nervous system. Cannon (1931) proposed the idea of involvement of adrenal medulla and sympathetic nervous system in fight, flight, and fright response. The responses to adrenalin stimulation are as follows:
  • Stimulation of α-adrenergic receptors leads to increased glycogenolysis (Arnal et al. 1986) in the liver and muscle, and glycolysis in muscle.

  • Stimulation of β-adrenergic receptors leads to enhanced lipolysis in adipose tissue, adrenocorticotropic hormone (ACTH) secretion from the pituitary gland, and increased cardiac output.


It is synthesised in the adrenal medulla in an enzymatic pathway shown in Fig. 1. Precursor molecule of adrenalin is tyrosine which further oxidized to L-3, 4-dihydroxyphenylalanine (L-DOPA). Decarboxylation of L-DOPA gives dopamine which is converted to norepinephrine by dopamine β-hydroxylase. The last step is the methylation of the primary amine of norepinephrine, catalyzed by the enzyme phenylethanolamine N-aminotransferase (PNMT). S-adenosylmethionine (SAMe) acts as the methyl donor. PNMT is mainly found in the chromaffin cells and in brain, but in very small amounts. In 1953, Coupland suggested that the adrenal cortex secreted a “methylation factor” that influenced the N-methylation of norepinephrine to form epinephrine. In 1959, Kirshner identified the adrenomedullary enzyme, PNMT (phenylethanolamine N-methyltransferase), responsible for the synthesis of epinephrine from norepinephrine.
Fig. 1

The enzymatic pathway for synthesis of epinephrine (adrenalin)


The expression of PNMT is dependent on high concentrations of adrenocortical glucocorticoids (Wurtman and Axelrod 1965) which are released from the adrenal cortex that reach the medulla via an intra-adrenal portal vascular system. In the adrenal medulla, these glucocorticoids regulate PNMT in two ways, transcriptionally and posttranslationally, by regulating the stability of the protein (Wong 2003). The levels of PNMT consequently affect the synthesis of adrenalin. In addition, epinephrine biosynthesis is activated by neural stimuli through the splanchnic innervation of the gland.

PNMT expression along with glucocorticoid levels were thought to be an important factor in defining the fate of undifferentiated cells as chromaffin cells but not as neurons. Recently, it has been observed that glucocorticoids receptor-deficient mice develop normal numbers of chromaffin cells, indicating that glucocorticoid signaling is not essential for forming the neuroendocrine phenotype in chromaffin cells and suggesting involvement of other factors (Huber et al. 2002).

Stress is also considered to be another stimulus for production of adrenalin. The main components of the stress system are hypothalamic CRH, as well as locus cereleus-norepinephrine and autonomic systems and their peripheral effectors. Thus, response of the endocrine system to stress is characterized by activation of the HPA axis and the sympathetic adrenomedullary system, which is associated with hypersecretion of adrenal hormones, particularly glucocorticoids and epinephrine (Pervanidou and Chrousos 2007). Production of adrenalin is stimulated by increasing the activity of tyrosine hydroxylase and dopamine β-hydroxylase which are key enzymes involved in catecholamine synthesis.

The reaction of the adrenal gland to stress has been studied in different animal models, using, for example, immobilization stress or cold stress where the release of catecholamines is stimulated by the splanchic innervation of the gland (Ehrhart and Bornstein 2008).

In stress conditions, adrenal cortex is stimulated by ACTH to release cortisol which consequently increases the expression of PNMT enzyme in chromaffin cells.

Chromaffin cells also possess nictonic acetylcholine receptors which bind to acetylcholine resulting in depolarization of the cell and influx of calcium through voltage-gated calcium channels. Increased levels of calcium in the cells trigger the exocytosis of chromaffin granules, hence increasing the level of adrenaline in the bloodstream.

Adrenalin does not exert negative feedback regulation unlike other hormones. Its action is terminated with reuptake into nerve terminal endings, some minute dilution, and metabolism by monoamine oxidase and catechol-O-methyl transferase.


Adrenalin is a key hormone playing role in flight or fight response. When brain senses some danger, adrenalin levels are elevated in bloodstream which is termed as adrenalin rush because its effects are executed very fast and once the danger is gone it may last up to an hour. To combat this hormone rush, “rest and digestive system” has to be activated which allows body to rest. There are medical conditions which results in overproduction of adrenaline such as surreptitious epinephrine administration, pheochromocytoma, and other tumors of the sympathetic ganglia.



  1. Arnall, D. A., Marker, J. C., Conlee, R. K., & Winder, W. W. (1986). Effect of infusing epinephrine on liver and muscle glycogenolysis during exercise in rats. American Journal of Physiology-Endocrinology and Metabolism, 250(6), E641–E649.CrossRefGoogle Scholar
  2. Canon, W. B. (1931). Studies on the conditions of activity in endocrine organs xxvii. Evidence that medulliadrenal secretion is not continuous. American Journal of Physiology, 98, 447–453.CrossRefGoogle Scholar
  3. Coupland, R. E. (1953). On the morphology and adrenaline-noradrenaline content of chromaffin tissue. Journal of Endocrinology, 9(2), 194–203.CrossRefGoogle Scholar
  4. Ehrhart-Bornstein, M., & Bornstein, S. R. (2008). Cross-talk between adrenal medulla and adrenal cortex in stress. Annals of the New York Academy of Sciences, 1148(1), 112–117.CrossRefGoogle Scholar
  5. Huber, K., Combs, S., Ernsberger, U., Kalcheim, C., & Unsicker, K. (2002). Generation of neuroendocrine Chromaffin cells from Sympathoadrenal progenitors. Annals of the New York Academy of Sciences, 971(1), 554–559.CrossRefGoogle Scholar
  6. Krishner, N. (1959). The formation of adrenaline from noradrenaline. Biochimica et Biophysica Acta, 24, 658–659.CrossRefGoogle Scholar
  7. Pervanidou, P., & Chrousos, G. (2007). Post-traumatic stress disorder in children and adolescents: From Sigmund Freud’s “trauma” to psychopathology and the (dys) metabolic syndrome. Hormone and Metabolic Research, 39(06), 413–419.CrossRefGoogle Scholar
  8. Wong, D. L. (2003). Why is the adrenal adrenergic? Endocrine Pathology, 14(1), 25–36.CrossRefGoogle Scholar
  9. Wurtman, R. J., & Axelrod, J. (1965). Adrenaline synthesis: Control by the pituitary gland and adrenal glucocorticoids. Science, 150(3702), 1464–1465.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Molecular Biology DivisionBhabha Atomic Research Centre, HBNIMumbaiIndia

Section editors and affiliations

  • Mystera M. Samuelson
    • 1
  1. 1.The Institute for Marine Mammal StudiesGulfportUSA