Endocrine Organisation Essay

Principles in the organization of the endocrine system, including the thyroid and adrenal glands

There is a wide range of hormones in the body, produced by several endocrine glands, amongst which are the adrenal glands and the thyroid gland. The thyroid gland has only two types of endocrine cell, follicular and parafollicular, which produce respectively thyroid hormone and calcitonin; however the adrenal gland has histologically different regions, the adrenal medulla and the adrenal cortex, which is further divided into the zona fasciculata, zona glomerulosa and zona reticularis. Unsurprisingly the adrenal glands therefore produce many more hormones than does the thyroid gland, amongst them noradrenaline, adrenaline, corticosteroids, mineralocorticoids and adrenal androgens. In these and other endocrine tissues, hormones are often made acutely from precursors and prohormones, which are beneficial in cases where proteolysis of the prohormone releases many hormones at once resulting in amplification, or releases hormones with similar effects, coordinating endocrine responses in the body. There are some common pathways for synthesis of hormone groups such as the catecholamines or cholesterol-derived steroid hormones. The biosynthesis of hormones is also closely linked to their storage. Many hormones are stored as intermediates in their production pathway, as in the thyroid gland, or as active hormones in vesicles ready to be released, guaranteeing a rapid large release of hormone upon stimulus, as in the adrenal medulla. These glands demonstrate another aspect of storing hormones, that of intracellularly in granules as well as in extracellular compartments such as follicles or blood. Some hormones, however, are released upon synthesis, and some demonstrate temporal patterns of release; in the case of cortisol release from the zona fasciculata, the release prepares the body for stresses such as waking and also occurs as cortisol is produced and diffuses out of the cell membrane. This shows that hormones may be released from cells via simple diffusion if they are hydrophobic, but release of hydrophilic hormones, i.e. the peptides and amines, is by mechanisms such as exocytosis. Depending on their solubility in plasma, circulatory transport may be as free dissolved hormone or bound to any of numerous plasma proteins; their method of transport affects the rate serum concentration rise and may affect degradation. Degradation of hormones can take place at several sites, including filtering by the kidney and breakdown in the liver; circulating plasma levels and cardiac flow to these organs therefore contribute to rate of hormone degradation. Regulation underpinning all these processes is of vital importance to the endocrine system as feedback loops such as control of the hypothalamic-pituitary-adrenal cortex axis (and, more rarely, feed-forward loops) tightly control hormonal production and secretion in a homeostatic system which continually seeks to return both metabolism and hormone levels to the normal ranges after a response to a temporary stress or changed condition.

There are several common pathways in hormone synthesis, two major ones being the catecholamine production pathway from phenylalanine and tyrosine, and the steroid production pathway, which uses cholesterol as a starting point for a myriad of active hormones including cortisol, oestradiol, testosterone and aldosterone. Many of these hormones are intermediates in the pathway for the production of other hormones, such as dopamine which is converted to noradrenaline, and DHEA, which is converted in two steps to testosterone. Other pathway intermediates are exploited as hormone precursors and are sometimes stored in large amounts so that active hormones can be quickly made and released upon stimulation, resulting in a faster rise in serum hormone levels. An example is the storage of cholesterol in mitochondria for steroid synthesis, and the production of colloid. Here the follicular epithelium produces thyroglobulin and secretes it into the follicle lumen where it is iodinated to make colloid. Thyroid-stimulating hormone can then activate lysosomal digestion of colloid to make T4. T4 is also often cited as a prohormone, as it is converted into the thyroid hormone T3 by iodothyronine deiodinases in the liver, CNS, skeletal muscle and other peripheral tissues¹⁰ in conditions where metabolism promotion is favourable, and it is T3 which is known to have the most widespread and important effects on the body. However T4 has its own hormonal effects on the body, as discussed below; this shows that precursors themselves are of use as well as for storage, rapid response and coordination purposes.

Precursors of peptide hormones also exist; these are called prohormones. As proteins are produced directly from mRNA in ribosomes and must later be processed in order for their structure to be changed, prohormones usually contain inactive copies of peptides or monomers which can be converted to active hormone. They are produced as preprohormones, with the peptide sequence(s) which will become a hormone surrounded by signalling sequences and other peptide chains. These are processed in both the rough endoplasmic reticula and Golgi apparatus, and proteolysis releases the active hormones. Thyrotrophin-releasing hormone (TRH) is made from pro-TRH, a hypothalamic prohormone which contains many TRH sequences and so upon cleavage can produce many TRH molecules at once. This will amplify the metabolic effects greatly, as a stimulus which makes one prohormone will result in multiple TRHs, resulting in a large rapid secretion of TSH released and ultimately a prolific synchronised T4 release. A more complex prohormone is proinsulin, a peptide of three different domains. The middle domain, C-peptide, is excised to produce two peptide chains which dimerise to form active insulin. POMC, pro-opiomelanocortin, is a prohormone that can give rise to four different...

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