Tuesday, November 17, 2015

Endocrinology: The Adrenal Medulla

Medullary hormones are tyrosine based, and have a DOPA precursor that turns into dopamine, and then eventually noradrenaline and adrenaline.


Creation of Medullary Hormones
Dopamine --> Noradrenaline --> Adrenaline
     -Most of the chromaffin output is adrenaline, then noradrenaline, and then dopamine.

Order of hormone production acronym: DNA

Production of dopamine and noradrenaline happen in the same synaptic vesicle. The creation of these medullary hormones are activated by the stimulation of ACh via the innervated preganglionic sympathetic fibers.

Each gland is supplied by the superior, middle and inferior suprarenal arteries:
  • Superior artery arises from the inferior phrenic artery
  • Middle artery arises from the abdominal aorta
  • Suprarenal artery arises from the renal artery
The adrenal medulla is an extension of the SNS, but the neurotransmitters are essentially neurohormones. 
The catecholamines have short half-lives:
     -Reuptake into presynaptic nerve terminals  
          -Noradrenaline transporter called uptake 1 or mechanisms

Inactivation of catecholamines are via catechol-o-methyl transferase (COMT) or monoamine oxidase (MAO) produced in the liver, kidneys and brain and located outside of the mitochondria. 
     -Products called metanephrins excreted in urine 

Process of Catecholamine Inactivation
Dopamine has two receptors: DR1 and DR2, and gets inactivated via prolactin. It can also be said that dopamine inhibits prolactin, but I think it makes sense both ways. However, it is more clear cut to say that dopamine inhibits prolactin. 


Adrenaline and noradrenaline use α and β receptors, which are 7 pass G-protein receptors with second messenger systems.
     -β 3 receptor types mediate adrenaline's effects in the newborn, by uncoupling oxidative phosphorylation in mitochondria via UCP1 (Uncoupling protein 1, a protein coding gene), enabling metabolism of triglycerides to generate heat rather than ATP to compensate for heat loss.


Essentially, all β receptors carry adenyl cyclase-cAMP as their secondary messenger system.

Sweat Glands:
  • Apocrine (e,g, hair follicles where sweat mixes with bacteria etc.) sweat glands are stimulated by noradrenaline 
  • Eccrine sweat glands (e.g. normal loss of heat from body surface) are innervated by cholinergic (ACh) postganglionic sympathetic nerve fibers. ]
-Stimulation of SNS is therefore associated with increased sweat through direct innervation of sweat glands whereas apocrine glands are stimulated by circulating catecholamines from the medulla. 

Catechols control the catecholamines by negative feedback
     -Inhibit the activity of tyrosine hydroxylase vital in catecholamine synthesis 
     -Therefore when catehcholamines are secreted after stimulation, from medullary chromaffin cells, intracellular catechol levels are depleted 
     -This decreases negative feedback so that catecholamine synthesis can be enhanced 

Glucocorticoids influence catecholamine production from the medulla directly, by stimulating tyrosine hydroxylase, dopamine β hydroxylase and PNMT (Phenylethanolamine N-methyltransferase) activity.


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