First Assignment: An introduction to Adrenocorticotropic hormone!

Adrenocorticotropic hormone (ACTH) is a peptide hormone. It is created from a 266 amino acid precursor known as proopiomelanocortin (POMC). ACTH is cleaved from POMC into a 39 amino acid long protein (Schlomo Melmed, 2011). This hormone is created in the adenohypophysus, or anterior pituitary, by corticotroph cells. ACTH can be detected in mammals such as dogs as early as the eighth week of the fetal stage, as Rathke's diverticulum (the predecessor of the anterior pituitary) extends to merge with the diencephalon (Schlomo Melmed, 2011).

As the term "Adrenocortico" suggests, ACTH is highly involved in mediation of function for the cortex of the adrenal glands. ACTH is released from the anterior pituitary into the blood where it stimulates the release of glucocorticoids such as the steroid hormone cortisol. Glucocorticoids are highly involved in digestion, the stress response, and physiological development (Bundgaard & Rehfeld, 2010). Thus, regulation for the release of ACTH is extremely important. ACTH works on a 24 hour circadian rhythm and peaks in the morning when it is time for the body to become awake and alert. The release of ACTH is stimulated by the release of corticotropin releasing hormone (CRH) from the hypothalamus. When ACTH is released into the blood, it binds to receptors of secretory cells in the adrenal cortex and triggers a G protein linked secondary messenger pathway. Glucocorticoids such as cortisol are then released into the blood stream where they cause gluconeogenesis from the liver. Glycogen is broken down and released as glucose into the blood stream where it provides energy for the body. Other functions of the glucocorticoids include moderating the metabolism of proteins, fat and carbohydrates, as well as controlling leukocyte production and inflammation during the immune response (Bundgaard and Rehfeld, 2010). The release of ACTH is mediated by the concentration of glucose and cortisol in the bloodstream. The hypothalamus registers when cortisol levels are peaking and thus releases less CRH, which in turn causes the stymied release of ACTH from the adenohypophysis.

The importance of glucocorticoids can be seen by the symptoms of patients who suffer from Cushing Syndrome, also known as hyperadrenocorticism. This condition is caused by an excess release of CRH in the hypothalamus or cortisol from the adrenal glands into the blood stream. The disease is often caused by a hormone secreting tumor in the glucocorticoid pathway (Constantine A. Stratikis, 2012). Since cortisol is highly involved in the metabolic production of fats and proteins, cushings syndrome causes rapid weight gain.

ACTH plays an extremely integral role in the metabolic pathway of the body. We still do not know many of its functions. Research has proven that synthetic ACTH can even be used to treat mild cases of epilepsy (Croiset & De Weid, 1992). There is so much still to be discovered about metabolic hormones such as ACTH, which is why I chose it as my favorite hormone!

Figure 1: The CRH, ACTH, and Cortisol secretory pathway showing how cortisol levels and stresses affect secretion. Taken from http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/adrenal/feedback.gif

References:

1) Melmed, S. (2011). Adrenocorticotropin. In The Pituitary (Third ed., pp. 47-50). San Diego, California: Blackwell Science.
2) Croiset, G., & De Wied, D. (1992). ACTH: A structure-activity study on pilocarpine-induced epilepsy. European Journal of Pharmacology, 229(2-3), 211-216.
3) Rehfeld, J., & Bundgaard, J. (2010). ACTH: Cellular Peptide Hormone Synthesis and Secretory Pathways. In Cellular Peptide Hormone Synthesis and Secretory Pathways (pp. 70-88). New York, New York: Springer.
4) Stratakis, C. (2012). Cushing Syndrome in Pediatrics. Endocrinology and Metabolism Clinics of North America, 41(4), 793-803.
5) http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/adrenal/feedback.gif