Adrenal Output

MINERALOCORTICOIDS (Zona Glomerulosa)

• Endogenous produced by zona glomerulosa.
• Aldosterone and others regulate intravascular volume and blood pressure.
• Aldosterone works on renal tubule.
• Aldosterone; Na+, bicarbonate (chloride) and H2O retention, decreasing resorption of potassium.
• Clients with Addison's disease have low minieralocorticoid production.
• Aldosterone levels are increasing in Conn's syndrome.
  

Formation of Mineralcorticoids

Physiologic Effects of Mineralocorticoids

Mineralocorticoids play a critical role in regulating concentrations of minerals - particularly sodium and potassium - in extracellular fluids. As described above, loss of these hormones leads rapidly to life-threatening abnormalities in electrolyte and fluid balance. Hyposecreation can lead to decreased blood volumethat can result in decreased cardiac output and hypotension. Hypersecreation can result in increased volume of extracellular fluid which leads to increased volume of the blood which can increase cardiac output ultimately resulting in hypertension.

The major target of aldosterone is the distal tubule of the kidney, where it stimulates exchange of sodium and potassium.

Three (3) primary physiologic effects of aldosterone:

1. Increased resorption of sodium: sodium loss in urine is decreased under aldosterone stimulation.
2. Increased resorption of water, with consequent expansion of extracellular fluid volume. This is an osmotic effect directly related to increased resorption of sodium.
3. Increased renal excretion of potassium.

Knowing these effects should quickly suggest the cellular mechanism of action this hormone. Aldosterone stimulates transcription of the gene encoding the sodium-potassium ATPase, leading to increased numbers of "sodium pumps" in the basolateral membranes of tubular epithelial cells. Aldosterone also stimulates expression of a sodium channel which facilitates uptake of sodium from the tubular lumen.

Aldosterone has effects on sweat glands, salivary glands and the colon which are essentially identical to those seen in the distal tubule of the kidney. The major net effect is again to conserve body sodium by stimulating its resorption or, in the case of the colon, absorption from the intestinal lumen. Conservation of water follows conservation of sodium.

Control of Aldosterone Secretion
Control over aldosterone secretion is truly multifactorial and tied into a spider web of other factors which regulate fluid and electrolyte composition and blood pressure. If the major effects of aldosterone are considered, it is rather easy to predict factors which stimulate or suppress aldosterone secretion.

The two (2) most significant regulators of aldosterone secretion are:

1. Concentration of potassium ions in extracellular fluid: Small increases in blood levels of potassium strongly stimulate aldosterone secretion.
2. Angiotensin II: Activation of the renin-angiotensin system as a result of decreased renal blood flow (usually due to decreased vascular volume) results in release of angiotensin II, which stimulates aldosterone secretion.

Other factors which stimulate aldosterone secretion include adrenocorticotropic hormone (short-term stimulation only) and sodium deficiency. Factors which suppress aldosterone secretion include atrial naturetic hormone, high sodium concentration and potassium deficiency.

GLUCOCORTICOIDS (Zona Fasciculata)

• endogenous released on diurnal cycle from zona fasciculata.
• exogenous are most potent anti-inflam medications available.
• synthetic drugs mb 20-100x more potent than endogenous cortisol.
• cortisol is principle endogenous one.
• binds to cell receptors;changes gene transcription and behavior of cells.
• promotes gluconeogenesist; increasing blood sugar to deal with stressor (trauma, infection, disease).
• regulates metabolism of proteins, carbohydrates, lipids.
• causes mild increase in blood pressure thru vasoconstriction.
• increase in circulating of neutrophils, HGB, RBC's.
• decrease circulating of lymphs including T cells, eosphils, basophilss, monosites, and macrophages.
• pharmacologic doses dramatically reduce accumulation of leukocytes and inhbits chemotactic signalling.
• also inhibits access of leukotrines to inflammation sites, intereferes with fixation of leukotrines and fibroblasts.
• inhibition of phospholipase A2; blocks release of arachadonic acid; no new prostaglandins or leukotrines.
• anti-inflammation effect due to decreased production of prostaglandins.
• also suppresses histamine release and kinin activity.
• metabolized by liver microsomal oxidizing enzymes.

Control of Cortisol Secretion
Cortisol and other glucocorticoids are secreted in response to a single stimulator: adrenocorticotropic hormone (ACTH) from the anterior pituitary. ACTH is itself secreted under control of the hypothalamic peptide corticotropin-releasing hormone (CRH). The central nervous system is thus the commander and chief of glucocorticoid responses, providing an excellent example of close integration between the nervous and endocrine systems.

Virtually any type of physical or mental stress results in elevation of cortisol concentrations in blood due to enhanced secretion of CRH in the hypothalamus. This fact sometimes makes it very difficult to assess glucocorticoid levels, particularly in animals. Observing the approach of a phlebotomist, and especially being restrained for blood sampling, is enough stress to artificially elevate cortisol levels several fold!

Cortisol secretion is suppressed by classical negative feedback loops. When blood concentrations rise above a certain theshold, cortisol inhibits CRH secretion from the hypothalamus, which turns off ACTH secretion, which leads to a turning off of cortisol secretion from the adrenal. The combination of positive and negative control on CRH secretion results in pulsatile secretion of cortisol. Typically, pulse amplitude and frequency are highest in the morning and lowest at night.
 
 

ACTH binds to receptors in the plasma membrane of cells in the zona fasiculata and reticularis of the adrenal. Hormone-receptor engagement activates adenyl cyclase, leading to elevated intracellular levels of cyclic AMP which leads ultimately to activation of the enzyme systems involved in biosynthesis of cortisol from cholesterol.

Physiologic Effects of Glucocorticoids

There seem to be no cells that lack glucocorticoid receptors and as a consequence, these steroid hormones have a huge number of effects on physiologic systems. That having been said, it can be stated that the best known and studied effects of glucocorticoids are on carbohydrate metabolism and immune function.

Effects on Metabolism

The name glucocorticoid derives from early observations that these hormones were involved in glucose metabolism. In the fasted state, cortisol stimulates several processes that collectively serve to increase and maintain normal concentrations of glucose in blood. These effects include: 

•Stimulation of gluconeogenesis, particularly in the liver: This pathway results in the synthesis of glucose from non-hexose substrates such as amino acids and lipids and is particularly important in carnivores and certain herbivores. Enhancing the expression of enzymes involved in gluconeogenesis is probably the best known metabolic function of glucocorticoids.

•Mobilization of amino acids from extrahepatic tissues: These serve as substrates for gluconeogenesis.

•Inhibition of glucose uptake in muscle and adipose tissue: A mechanism to conserve glucose.

•Stimulation of fat breakdown in adipose tissue: The fatty acids released by lipolysis are used for production of energy in tissues like muscle, and the released glycerol provide another substrate for gluconeogenesis.

Effects on Inflammation and Immune Function

Glucocorticoids have potent anti-inflammatory and immunosuppressive properties. This is particularly evident when they administered at pharmacologic doses, but also is important in normal immune responses. As a consequence, glucocorticoids are widely used as drugs to treat inflammatory conditions such as arthritis or dermatitis, and as adjunction therapy for conditions such as autoimmune diseases.

Other Effects of Glucocorticoids
Glucocorticoids have multiple effects on fetal development. An important example is their role in promoting maturation of the lung and production of the surfactant necessary for extrauterine lung function. 

Several aspects of cognitive function are known to both stimulate glucocorticoid secretion and be influenced by glucocorticoids. Fear provides an interesting example of this. Fear-inducing stimuli lead to secretion of glucocorticoids from the adrenal gland, and treatment of phobic individuals with glucocorticoids prior to a fear-inducing stimulus can blunt the fear response.

Excessive glucocorticoid levels resulting from administration as a drug or hyperadrenocorticism have effects on many systems. Some examples include inhibition of bone formation, suppression of calcium absorption and delayed wound healing. These observations suggest a multitide of less dramatic physiologic roles for glucocorticoids.

Next: Catacolemines the Forgotten Adrenal Hormones..............................................