Adrenal Glands

Hello :) In this post we'll be learning about the adrenal glands. We'll discuss the anatomical structure of the adrenal gland as well as the actions of the hormones that this gland produces. We'll also take a detailed look at the synthesis of glucocorticoid hormones and explain the regulatory mechanisms which control the synthesis and secretion of adrenocorticoid and catecholamine hormones. We'll also discuss hypo- and hyperadrenocorticism and list the different types of adrenergic receptors and the response they bring about following activation. Enjoy!

Structure 

The adrenals are paired glands located at the superior poles of the two kidneys and are composed of an outer cortex (80%) and inner medulla (20%).

The cortex is composed of three different histological layers:

• zona glomerulosa (thinnest and outer most): this secretes mineralocorticoids (eg. aldosterone)
• zona fasciculata (middle and thickest): secretes glucocorticoids (eg. cortisol) and a smaller quantity of sex hormones.
• zona reticularis (inner most): secretes sex hormones (androgens which are converted to oestrogens) and a smaller quantity of glucocorticoids

Each of these layers produces different hormones. 

Adrenocorticoids

Hormone Synthesis:

The Adrenal Cortex hormones (adrenocorticoids) share a common mechanism of synthesis. Steroid hormones all come from a cholesterol precursor. Low density lipoproteins (LDLs) (see this post) are responsible for 80% of the cholesterol delivered to the adrenal glands. The LDL-receptor complex is endocytosed and digested by lysosomes. It is then transferred to the inner mitochondrial membrane by steroidogenic acute regulatory (StAR) proteins. The substance is then converted to pregnenolone by the cytochrome P450scc (side chain cleavage) enzyme. Pregnenolone then enters the endoplasmic reticulum and undergoes multiple complex steps to be converted to mineralocorticoids, glucocorticoids or androgens. The rate limiting step of this whole process is the movement of cholesterol into the mitochondria by the StAR protein. 

Glucocorticoids

Actions:

Glucocorticoids have a range of actions which help to maintain homeostasis. They work by binding to specific glucocorticoid receptors in the cell nucleus and this alters gene expression. Basically, their function is to mobilise body fuels, particularly during times of stress and their effects are catabolic. In terms of carbohydrate metabolism, they increase gluconeogenesis and glycogenolysis and enhance the actions of glucagon. This increases blood glucose concentration. In addition, these hormones inhibit glucose uptake and utilization by peripheral tissues. This slows down the consumption of blood glucose.

 In terms of protein metabolism, the hormones stimulate protein catabolism and inhibit protein synthesis, however, the brain and cardiac muscle is protected. 

In terms of fat metabolism, they enhance lipolysis and this causes free fatty acids to be released into the blood stream. Plasma cholesterol concentrations also increase and fat deposits are redistributed. 

Glucocorticoids also induce negative calcium balance through inhibition of intestinal absorption and increased renal excretion. They also inhibit osteoblast function and this may result in osteoporosis.

These hormones also diminish the inflammatory and immune response. 

Mineralocorticoids (Aldosterone):

Action

Aldosterone binds to receptors in the cytosol of the principal cells of the late distal tubule and collecting ducts of the kidney. The binding of this hormone stimulates the synthesis and opening of sodium and potassium ion channels on the apical membrane. On the basolateral membrane it causes the synthesis and insertion of Na/K pumps. These two actions simultaneously increase sodium reabsorption and potassium secretion.

Catecholamines

Action

Catecholamines include adrenaline and noradrenaline (also called epinephrine and norepinephrine, respectively). These hormones are used as neurotransmitters by the sympathetic division of the autonomic nervous system. These substances bind to adrenergic receptors which are present in most cells of the body. There are four subtypes of adrenergic receptors and each responds differently to the catecholamines:

• ·α1 : these are located on the postsynaptic nerve endings. They cause vascular smooth muscle contraction which results in vasoconstriction and increased blood pressure.

• ·     α 2: these are found on pre- and post-synaptic nerve endings. They inhibit noradrenaline, have mixed effects on smooth muscle and cause vasodilation.

• ·          β1: these are found in the heart. They have positive inotropic (cause an increase in the force of contraction) and chronotropic (increase heart rate) cardiac effects. They also increase renin secretion and adipocyte lipolysis.

• ·          β2: Found in skeletal muscle, arterioles and bronchioles. They cause smooth muscle vasodilation, bronchodilation and uterine relaxation.

 

Regulation of Synthesis and Secretion of Catecholamines and Adrenocorticoids

Adrenocorticotropic Hormone (ACTH) primarily stimulates the synthesis of glucocorticoids and androgens. In the short term it causes a StAR mediated increase in cholesterol delivery to the mitochondria. In the long term it stimulates the synthesis of steroidogenic enzymes. The secretion of ACTH is controlled by corticotropin-releasing hormone (CRH) which is released by the anterior pituitary gland (See this post).  

Disorders of the Adrenal Glands

Hypoadrenocorticism:

This is also known as Addison’s disease in dogs and is characterised by significantly reduced cortisol and aldosterone levels. There are three types of hypoadrenocorticism:

·         Primary: this may be idiopathic (spontaneous), immune mediated or drug induced destruction of the adrenocortical tissue.

·         Secondary: due to impaired hypothalamic-pituitary function

·         Iatrogenic: this is when normal secretion may be impaired following the withdrawal of glucocorticoid therapy. This is because it takes time for the adrenal cortex to start producing its own hormones again.

Clinical signs include: hyponatraemia/hyperkalaemia, hypovolaemia and dehydration, vomiting or diarrhoea, and hypothermia.

Hyperadrenocorticism:

This is also known as Cushing’s Syndrome in dogs and results in the excess secretion of hormones from the adrenal cortex. There are three forms of this syndrome:

• Pituitary Dependent (80%): Excessive ACTH secretion by the pituitary (most commonly because of a tumour) results in bilateral adrenal hyperplasia which causes excess cortisol secretion and the failure of the negative feedback system of ACTH. 
• Adrenal dependent 
• Iatrogenic

Clinical signs include: muscle wasting and weakness as a result of increased protein catabolism and decreased protein synthesis; secondary infection due to a compromised immune system; abdominal distention due to the redistribution of fat deposits and polyphagia causing weight gain; alopecia because hair growth is inhibited; as well as panting and respiratory changes because of exercise intolerance and muscle wasting from protein catabolism.

That's it for this post, if you have any questions please feel free to ask :)