Hormones are certain chemical compounds secreted by ductless glands in an animal's body. They are released directly into the blood but their impact is seen only on their target organs. Some of these hormones called trophic hormones are responsible for regulating the function of other ductless glands. In this article, we are going to learn about the trophic hormone ACTH, its functions and related disorders in detail.
ACTH is an acronym for an adrenocorticotropic hormone which is produced and released by the anterior pituitary gland. It is also referred to as corticotropin. Its functions involve stimulating the production of hormones from the adrenal cortex, specifically glucocorticoids.
The synthesis of ACTH is triggered when the pituitary gland is acted upon by the Corticotropin-releasing hormone present in the hypothalamus.
ACTH is observed to be synthesised in the basophilic cells present in the anterior pituitary gland from a molecule called pre-proopiomelanocortin (also written as pre-POMC). The signal peptide is discarded during translation that leads to the formation of a 241- amino acid polypeptide called POMC. It is observed that POMC then sequentially undergoes some translational modifications like phosphorylation and glycosylation.
The end product is then cleaved by enzymes known as endopeptidases to yield a range of polypeptide fragments with varying functionality. One of these fragments includes our hormone of concern- the ACTH.
Adrenocortical cells in the adrenal gland are the target cells for ACTH. The secreted ACTH, when attached with these cells, activates an enzyme called adenylyl cyclase in the cell membrane of the cell which in turn produces cAMP.The cAMP is known to activate various pathways that result in the formation of adrenocortical hormones. The pathway also leads to the activation of a protein called Kinase A which is necessary to convert cholesterol to pregnenolone which acts as a rate limiting step for the synthesis of adrenocortical hormones.
ACTH is involved in stimulating the secretion of the glucocorticoid hormones, especially cortisol which is steroidal in nature from the adrenal cortex cells.
ACTH is actively involved in stimulating the uptake of lipoproteins into the cortical cells resulting in the enhanced availability of cholesterol in the cells present in the adrenal cortex.
It plays a crucial role in the regulation of metabolism in the body which primarily involves bone resorption, protein catabolism, hyperglycemia and lipolysis.
Recently, it has been observed that secretion of ACTH has immune-suppressing effects in the body.
ACTH stimulates secretions of dehydroepiandrosterone, also referred to as DHEA. DHEA is considered as as a secondary sex hormone that is further used for synthesis of androgens and ultimately leads to spermatogenesis.
It has been also observed that ACTH often has anabolic effects on muscles and bones.
Levels of ACTH are observed to be generally high in the morning especially during the time when one wakes up.Then it gradually falls as the day progresses. It is at its lowest level during the time we sleep. This is also referred to as the diurnal or the circadian rhythm.
As we have learnt above, the secretion of ACTH primarily is dependent on the intercommunication of three parts of the body which includes hypothalamus, the adrenal gland and finally the pituitary gland. Together they are referred to as the HPA or the hypothalamic-Pituitary-Adrenal axis. When blood cortisol levels are lower than normal, a special group of cells present in the hypothalamus release the corticotropin-releasing hormone which in turn enables the pituitary gland to release ACTH for circulation in the bloodstream.
Now increased levels of ACTH are observed by the receptors of adrenal gland. This leads to the stimulation of cortisol that is secreted into the bloodstream. Increasing blood cortisol levels now start to negatively impact the secretion of corticotropin releasing hormone from the hypothalamus. This process is referred to as long loop inhibition. It also slows down the secretion of ACTH from the pituitary gland by a process called short loop inhibition.
As a result, ACTH levels gradually decrease in blood and ultimately blood cortisol levels also start to reduce. This whole cycle is referred to as the negative feedback loop.
It is crucial to note that stress(physical and psychological in nature) enables the production of ACTH that enhances blood cortisol levels.
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ACTH hormone does not cause any direct disorders in the human body. However, since it plays an important role in the regulation of other crucial hormones like cortisol, aldosterone, androgens; the levels of ACTH in blood will directly lead to the amount of other related hormones present in the blood. Increased or reduced amounts of these hormones ultimately lead to the various disorders observed.
The side effects of excess ACTH hormone are primarily due to the increased blood cortisol levels. Increased ACTH levels are due to.
Cushing’s Syndrome− This is the most commonly seen reason for increased ACTH hormone. It is primarily caused by a tumour that is not cancerous referred to as Adenoma present in the pituitary gland that leads to the production of excess ACTH.
However, in rare cases, a tumour outside the pituitary gland may also produce ACTH in excess amounts which is referred to as ectopic ACTH hormone tumour.
Insufficiency in adrenal gland functioning commonly known as the Addison’s disease may raise ACTH levels in the blood to replenish the decreased blood cortisol levels.
Similarly congenital adrenal hyperplasia, a genetic disorder responsible for insufficient cortisol production, also induces excess ACTH levels in the blood.
Obesity may be observed, especially in the upper body. Roundness of face and accumulation of fat in the throat region is a characteristic feature.
In the abdomen,buttocks or the thigh region, stretch marks may be seen.
Skin becomes fragile.
Reduced sexual drive in men and irregularities in the menstrual cycle of women may occur.
This condition may occur due to −
Cushing’s syndrome- This is related to an endogenous tumour present in adrenal gland or long term usage of medication with steroid doses.
Conditions that negatively impact the pituitary gland like hypopituitarism etc.
Commonly seen effects include anorexia, which refers to lack of appetite.
Low blood sugar and potassium levels may be observed in the affected individuals. .
Females may observe reduced hair growth in armpits and pubic region.
Varied emotional responses are seen. Variations could range from depression to psychosis.
We learn about the significance of the ACTH hormone from the above sections. It is a key hormone that is responsible for the secretion of other vital adreno-cortical steroid hormones like cortisol that is responsible for the body metabolism and specially the body’s response to stress. We study how ACTH is synthesised and finally learn about its functions and the disorders that are caused due to its improper levels in the human body.
Q1. What is meant by catabolism and anabolism?
Ans. Catabolism is referred to as the process that involves breaking down complex molecules into simpler ones. The process ultimately releases energy. Anabolism on the other hand involves smaller molecules combining to form a larger and complex molecule. This process requires energy.
Q2. What are the various types of hormones?
Ans. Hormones are generally classified into two types. The first one is referred to as peptide hormones which are composed of amino acids and are dissolved in water. Examples include insulin. The second type is referred to as steroid hormones that are fat soluble. Sex hormones are some examples.
Q3. What is the circadian rhythm?
Ans. It can be attributed as a natural process that includes cyclical changes in the physical,mental and also behavioural changes under a 24 hour time span.
Q4. What is the significance of the posterior pituitary?
Ans. This region of the pituitary is not glandular as compared to the anterior region and instead consists of a few axon projections directly from the hypothalamus.It acts as an important region for the secretion of oxytocin and vasopressin.
Q5. What does the medulla region of adrenal gland produce?
Ans. The major hormones secreted by the medulla region of the adrenal gland are adrenaline and noradrenaline which play a role in the flight or fight response of the body.
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