Stress Hormones: Function & Diseases

Stress hormones can be roughly divided into the two groups of glucocorticoids and catecholamines. The most important representatives are the hormones adrenaline and cortisol, which are produced in the adrenal cortex. Stress hormones are thought to ensure survival by providing an excess of energy.

What are stress hormones?

In stressful situations, the body secretes stress hormones. Such stressful situations include hard physical work, competitive sports, or psychological stress such as fear of loss, failure, or death. Serious illnesses can also promote the release of stress hormones. In addition to catecholamines such as adrenaline and noradrenaline, glucocorticoids such as cortisol are also among the stress hormones. All stress hormones have effects on metabolism and are primarily intended to provide energy to help the body cope with a stressful situation. The catecholamines are the better known group of stress hormones. The fact that glucocorticoids are less well known is probably due to their delayed action. Unlike catecholamines, they exert their effects through regulation in gene expression rather than via G-protein-coupled receptors. Among the most important stress hormones from the two groups are epinephrine and cortisol.

Anatomy and structure

Epinephrine is chemically expressed as (R)-1-(3,4-dihydroxyphenyl)-2-(N-methylamino)ethanol, making it one of the catecholamines. The effective variant of epinephrine corresponds to a stereochemical (R) configuration. Biosynthesis proceeds via the α-amino acids L-phenylalanine and L-tyrosine. Hydroxylation by L-DOPA and decarboxylation to dopamine occurs. This is followed by enantioselective hydroxylation to norepinephrine. Norepinephrine is released from the adrenal medulla and appears in the sympathetic nervous system as a transmitter. Only N-methylation of the norepinephrine thus formed yields epinephrine proper. Cortisol, on the other hand, is formed from cholesterol. In the adrenal cortex, pregnenolone is synthesized via a six-electron oxidation. This is followed by cholesterol translocase. Pregnenolone then leaves the mitochondrion of the adrenal cortex and is transformed to progesterone by 3β-hydroxysteroid dehydrogenase and isomerase. Progesterone is transformed to 17α-hydroxyprogesterone by the enzyme 17-steroid hydroxylase. Hydroxylation occurs again, yielding 11-deoxycortisol. Steroid 11beta-hydroxylase transforms this substance to cortisol.

Function and roles

Stress hormones are thought to ensure survival in stressful situations by providing energy. In prehistoric times, survival in a stressful situation was ensured primarily by fight and flight, with both survival strategies requiring an excess of energy. The hypothalamus is the highest instance in the release of stress hormones. This is where the precursors of stress hormones – the substances CRH and ACT – are formed. These substances stimulate the synthesis and release of hormones from the adrenal cortex by stimulating hormone-producing cells. In sudden and short-lasting stress, adrenaline is of great importance in the context of survival, because the effectiveness of catecholamines is much more sudden than that of glucocorticoids. Adrenaline binds to receptors and does not operate at the level of gene expression. The hormone exhibits various effects on the nervous system, cardiovascular system, musculature, and gastrointestinal tract. For example, adrenaline raises blood pressure, increases heart rate and inhibits digestion. The hormone exerts its effect by binding to adrenoreceptors. In addition, adrenaline enables the rapid provision of energy through fat breakdown. Due to the blood flow regulating effects, a decentralization of the circulation occurs. The vital organs can thus still be supplied with blood in the event of an accident, even after a major blood loss. Apart from this, adrenaline has a pain-inhibiting effect and thus makes it possible to go beyond one’s own limits. In the case of long-term stress, on the other hand, the body secretes glucocorticoids such as cortisol. The release of these stress hormones is more sluggish, so they would have no effect during sudden stress. Cortisol activates degradative metabolic processes and in this way provides the body with energy-rich compounds.

Diseases

Some of the best-known diseases related to stress hormones are Cushing’s disease and Addison’s disease.In Cushing’s disease, there is an overactivity of cortisol stimulation by the precursor ACTH. This leads to hypercortisolism. This hypercotisolism is usually caused by a tumor of the pituitary gland. The tumor in the pituitary gland overstimulates the ACTH-producing cells. Decreased muscle mass and weight gain determined the clinical picture. Increased blood pressure, increased bone fragility and severe thirst may also develop. Cushing’s syndrome is to be distinguished from this disease. Also in the context of this disease the mentioned symptoms can appear. However, a Cushing’s syndrome does not have to correspond to a tumor on the pituitary gland. In the context of the syndrome, the adrenal cortex produces much more autonomously too much cortisol without being stimulated to do so. The syndrome is caused by external influences, such as glucocorticoid use. Unlike Cushing’s disease or Cushing’s syndrome, Addison’s disease is an underactivity of the adrenal cortex. This disease exists in an autoimmunological form. This means that antibodies are formed against the hormone-producing cells of the adrenal cortex and ultimately cause these cells to be destroyed. However, Addison’s disease can also occur in the context of other diseases, such as storage disorders, as part of syndromes such as Waterhouse-Friedrich syndrome, or as a reduction in function due to tumor metastases.