Figure 1 - The structure of magnesium.

The inner and middle shells, K and L, of magnesium are complete and have 2 and 8 electrons respectively.

The outer shell M has only two electrons- It is particularly important for the reactive capacity of magnesium

Table 1 - The effects of magnesium deficit on calcium- phosphorus and potassium

In J. Durlach, Les contrôles neuro-hormonaux du métabolisme du magnésium et leurs conséquences cliniques. Rev. Franç. Endocrinol. Clin. 21, 6, 507-524, 1980.

These may range from forms with calcinosis and potassium deficit to forms that exhibit no calcium-phosphorus or potassium problem.

Figure 2 - Feedback loop for the medullary-adrenal regulation of magnesemia

In J. Durlach, Les contrôles neuro-hormonaux du métabolisme du magnésium et leurs conséquences cliniques, Rev. Franç. Endocrinol. Clin., 21, 6, 507-524, 1980.

Hypomagnesemia induces a medullary-adrenal hyperadrenalism that causes compensatory high blood levels of magnesium. Inversely, these high levels (possibly due to hyperadrenalism) cause medullary-adrenal hypoadrenalinism with compensating hypomagnesemia.

The system is defective when the lipolytic effects of large doses of adrenalin replace the hormone's action of raising blood magnesium with a lowering effect. This event is all the more harmful in that, conversely, magnesium deficit enhances the toxicity of adrenalin.

Figure 3 - Endocrine feedback loops with the humoral effects of disturbances in magnesium metabolism

In J. Durlach, Les contrôles neuro-hormonaux du métabolisme du magnésium et leurs conséquences cliniques. Rev. Franç Endocrinol. Clin., 21, 6, 507, 524, 1980.

Hypocalcemia causes a hyperparathyroidism and a hypomedullothyroidism which produce a compensatory increase in blood calcium levels. Inversely, hypercalcemia induces a hypoparathyroidism and a hypermedullothyroidism which cause a compensatory lowering of blood calcium

Low cellular potassium induces a compensatory hyperinsulinism that raises potassium levels while high cell potassium induces a hypoinsulinism that lowers cell potassium.

These systems are defective in magnesium deficit (MD), either because of a blocking of reactive secretions (earlier in the case of the parathyroid glands than for the beta ceils of the pancreas) or because of a reduced receptor sensitivity (especially in bone).

In magnesium overload (MO) the reduction in calcium levels may overshoot its goal and the hypoinsulinism may not occur (forms with hypokalemia).

Figure 4 - General diagram of the endocrine feedback control of humoral disorders due to alterations in magnesium metabolism

In J. Durlach, Les contrôles neuro-hormonaux du métabolisme du magnésium et leurs conséquences cliniques Rev Franç Endocrinol. Clin., 21, 6, 507, 524, 1980.

Four types of glands are involved in magnesium homeostasis: medullary-adrenal, parathyroid, medullary-thyroid and the beta cells of the islets of Langerhans

It is interesting to note that the three types of glands that control calcium and potassium metabolism (medullary-thyroid. parathyroid and the beta pancreas) exercise in parallel fashion added regulatory effects on magnesium metabolism.

The PTH-CT couple is particularly involved in exchanges between the extracellular compartment and hard tissues Adrenalin and insulin are involved with exchanges with soft tissues.

Proportionally sensitive to their specific stimuli, these endocrine controls become significantly involved only in the case of large changes in magnesium levels.

Defects in the system occur sometimes through excessive responses, sometimes through insufficient ones.

Figure 5 - Neuro-endocrine regulatory feedback loops for changes of peripheral Cyclic AMP (cAMP) levels secondary to variations in magnesium stores.

In J. Durlach, Aspects cliniques et biologiques du déficit magnésique chronique primaire. Feuilliets de Biologie, 23. 129. 61-84, 1982.

Magnesium deficit (MD) directly causes a reduced production of cAMP in the cell, probably by inhibition of Mg-dependent adenylate cyclase.

The organism responds by stimulation of the presynaptic sympathetic fibers ( and of the medullary-adrenal glands which produce catecholamines (especially noradrenalin) which in turn stimulate the cAMP-responsive beta receptors.

Magnesium overload (MO), like an excess of catecholamines, directly causes an increased production of cAMP in the cell, probably by stimulation of adenylate cyclase.

The organism reacts by slowing the response of the sympathetic fibers and of the medullary-adrenal glands which inhibits production of catecholamines and therefore of cAMP.

Figure 6 - A hypothetic taurine regulatory feedback loop for changes in the levels of peripheral cyclic GMP secondary to variations in magnesium stores.

In J. Durlach, Aspects cliniques et biologiques du déficit magnésique chronique primaire. Feuillets de biologie, 23, 129, 61-84, 1982.

Magnesium deficit (MD) directly causes an increase in cGMP in the cell, probably by stimulating Ca-dependent guanylate cyclase.

Different responses of the organism to magnesium deficiency (alpha stimulation, increased levels of acetylcholine and serotonin, H₁ stimulation) further increase the levels of cGMP.

The regulatory response of the organism derives from an increased influx of taurine into the cell. This effect could itself depend on beta stimulation, a classic inducer of taurine entry into the cell. There, taurine would inhibit guanylate cyclase, thus reducing the increased levels of cGMP.

The effects of magnesium overload (MO) on the levels of cGMP should be the reverse. One can imagine that, through a slowing of beta responses, it would cause an outflux of intracellular taurine. This would reduce its inhibitory effect on the production of cGMP whose levels would then increase. In any case, reduction of taurine during magnesium overload has not yet been the subject of any direct verification, whence the hypothetical character of the regulatory feedback loop for cGMP.

One must still note that, were this schema shown to be accurate, beta effectors would appear to regulate opposing anomalies of cyclic nucelotides during alterations of magnesium metabolism.

Figure 7 - The role of insulin, adrenalin and taurine in cellular homeostasis during magnesium deficit

See J. Durlach, V. Durlach, Speculations on hormonal controls of magnesium homeostasis: a hypothesis. Magnesium. 3,3, 109-131, 1984.

During magnesium deficit, hypersecretion of adrenalin and insulin participates in the homeostasis of magnesium levels in extracellular fluids without exercising this regulatory action at the expense of the equilibrium of the intracellular compartment. Parallel variations in their secretion help maintain the constancy of the levels in intracellular magnesium in the soft tissues: insulin increases magnesium translocation toward the cell, while adrenalin, probably by its beta component, reduces it. In like fashion, the opposing effects of the two hormones on the levels of cyclic AMP (cAMP) exercise a similar equilibrating action.

Hypersecretion of the two hormones exposes the patient to three types of harmful secondary effects: membrane depolarization, phosphocalcium overload (Calcinosis) and an increase in the levels of cyclic GMP( ä cGMP).

The intervention of taurine regulation thus acquires all the more importance. Hypersecretion of adrenalin and insulin favors in fact the intracellular influx of taurine (i.e. TA). In addition to its own magnesium sparing effects, taurine can exercise powerful antagonistic actions in the cell against the various harmful side effects of the hypersecretion of adrenalin and insulin by stabilizing membranes, chelating Ca²⁺ and reducing the levels of cyclic GMP.

Figure 8 - The principal hormonal and neurohormonal control elements of magnesium homeostasis

See J. Durlach, V. Durlach, Speculations on hormonal controls of magnesium homeostasis: a hypothesis. Magnesium, 3,3, 109-131, 1984.

The hormones and neurohormones implicated in magnesium homeostasis belong to three groups.

1 - The parathyroid hormone-calcitonin couple mainly controls exchanges between the extracellular compartment and the hard tissues. Certain digestive polypeptide hormones must also be involved, but their role still remains poorly defined.

2 - Adrenalin and insulin preside especially over exchanges between extracellular compartments and the soft tissues.

3 - The third group includes taurine and L-gamma-glutamyl-taurine. Taurine, secreted in humans by the kidney, and perhaps L-gamma glutamyl-taurine which may be a new parathyroid hormone, may play an important role that is closely linked with that of the adrenalin-insulin group. Indirectly they may oppose the harmful intracellular effects of hypersecretion of adrenalin and insulin thanks to their ability to stabilize membranes, chelate calcium and reduce levels of cyclic GMP. They may perhaps also exercise a direct magnesium-sparing effect.