It can result in low levels of calcium in the blood hypocalcaemia. It is usually treated medically with oral calcium and vitamin D analogues but the availability of parathyroid hormone replacement therapy may change the approach to treatment for some patients.
About Contact Events News. Search Search. You and Your Hormones. Students Teachers Patients Browse. Human body. Home Hormones Parathyroid hormone. Parathyroid hormone Parathyroid hormone is secreted by the parathyroid glands and is the most important regulator of blood calcium levels. Alternative names for parathyroid hormone PTH; parathormone; parathyrin What is parathyroid hormone? In contrast, overproduction of PTH can result in hyperparathyroidism. Answer the question s below to see how well you understand the topics covered in the previous section.
Skip to main content. Module 1: The Endocrine System. Search for:. The Parathyroid Glands Learning Objectives By the end of this section, you will be able to: Describe the location and structure of the parathyroid glands Describe the hormonal control of blood calcium levels Discuss the physiological response of parathyroid dysfunction. View the University of Michigan WebScope to explore the tissue sample in greater detail.
Critical Thinking Questions Describe the role of negative feedback in the function of the parathyroid gland. Explain why someone with a parathyroid gland tumor might develop kidney stones. Low blood calcium levels initiate the production and secretion of PTH. PTH increases bone resorption, calcium absorption from the intestines, and calcium reabsorption by the kidneys. As a result, blood calcium levels begin to rise. This, in turn, inhibits the further production and secretion of PTH.
A parathyroid gland tumor can prompt hypersecretion of PTH. This can raise blood calcium levels so excessively that calcium deposits begin to accumulate throughout the body, including in the kidney tubules, where they are referred to as kidney stones. Licenses and Attributions. Numerous secretory granules are seen at the luminal surface. The serum PTH level is higher and parathyroid chief cells show hyperfunction morphologically. Accumulating evidence suggests that parathyroid follicles are developed to meet the need for storage of PTH that can later be released into the blood.
In mammalian development, the parathyroid glands, together with the thymus, thyroid, and ultimobranchial bodies, are derived from the third and fourth pharyngeal pouches Fig.
In humans, the superior parathyroid glands are derived from the endoderm of the fourth pharyngeal pouches. Later in development, the inferior glands separate from the thymus and come to lie caudal to the thyroid and superior parathyroid glands. The relationship of the inferior parathyroid glands and the thymus explains the variable position of the inferior parathyroid glands, as the thymus has a long course of descent into the superior mediastinum and frequently presents in ectopic locations.
This embryologic development also explains the many possible locations of ectopic parathyroid tissue or supernumerary glands [ 13 , 15 ]. Diagram of normal pharyngeal organ development. The superior parathyroid glands and ultimobranchil body derives from the 4th pharyngeal pouch. The inferior parathyroid glands originate from the 3rd pharyngeal pouch along with the thymus.
In mice, there is only one pair of parathyroid glands, which originate from the endoderm derived epithelial layer that lines the third pharyngeal pouches; this is homologous to the inferior parathyroid glands in humans. The mouse parathyroid glands develop with the thymus from the 3rd pharyngeal pouch endoderm beginning at embryonic day E E8. The 3rd pharyngeal pouches become visible by E9. The parathyroid and thymus can be recognized at E The parathyroid glands become situated posterior to the lobes of the thyroid, whereas the thymus descends further in the direction of the heart.
Thus, the organogenesis of the parathyroid and thymus are closely linked at the early stage of development. At this stage, the parathyroid glands show a high degree of vascularity, and their innervation is derived from the cervical sympathetic ganglia and branches of the vagus nerve.
Expression of PTH gene occurs as early as at E In addition to the endodermal cells of the pharyngeal pouches, cells originating from the neural crest of rhombomeres 6 and 7 of the hindbrain also contribute to the anlage of the parathyroid glands [ 24 ].
The molecular signaling pathways that are involved in determining the differentiation of the pharyngeal pouch endoderm into parathyroid cells are being elucidated by studies of patients with hypoparathyroidism and appropriate mouse models.
Studies in mice have demonstrated that the transcription factor encoded by Gcm2 is a key regulator of parathyroid gland development. The null mutation of Gcm2 in mice leads to agenesis of the parathyroid glands from E12 onwards [ 10 , 23 ].
At E Loss of PTH secreting cells is caused by increased cell death [ 10 ]. In the chick Gcm2 is expressed in the third and fourth pouch, reflecting the development of parathyroid glands from both of the 3rd and 4th pharyngeal pouches [ 13 ]. In humans, homozygous inactivating mutations in Gcm2 have been related to the familial autosomal recessive and dominant isolated forms of hypoparathyroidism.
Gcm2 mutated individuals typically exhibit undetectable or residual PTH levels. Evidence suggests that some parathyroid adenomas might be associated with a dysregulation of Gcm2 expression.
Both reduced and enhanced Gcm2 expression levels are found in some human parathyroid adenoma [ 25 ]. The expression of Gcm2 is restricted to the parathyroid glands, and if this gene is mutated, the parathyroid glands fail to form. Therefore, Gcm2 is the key regulating transcription factor for parathyroid gland development.
The continued expression of high levels of Gcm2 in mature parathyroid glands suggests that it is required for maintenance of parathyroid cell differentiation. The discovery of Gcm2 as an essential transcription factor for parathyroid gland development disclosed another, unexpected source of circulating PTH, the thymus [ 10 ]. A recent phylogenetic analysis of Gcm2 has led to a new theory that parathyroid glands in tetrapods are transformed from the gills of fish during evolution [ 11 , 26 , 27 ].
It has long been held that the parathyroid glands and PTH evolved with the emergence of the tetrapods, reflecting a need for new controls on calcium homeostasis in terrestrial, rather than aquatic, environments. This event freed the tetrapods from relying on calcium uptake from the water by giving them the ability to internally regulate their serum calcium levels.
Amphibians have parathyroid glands, whereas fish do not have these glands. Recent studies have indicated that the gill buds are homologous structures that play a similar role in controlling calcium levels [ 11 , 26 , 27 ]. Gcm2 is expressed in the pharyngeal arch epithelium starting in the 2nd pouch before extending to the other pouches, and later in the internal gill buds in both zebrafish and dogfish [ 11 ].
Loss of Gcm2 results in loss of the gill buds [ 11 , 26 ], and also lead to cartilage defects [ 27 ]. It is therefore proposed that the internalization of Gcm2 positive region during the move to land lead to the formation of the tetrapod parathyroid gland.
The tissue origin of Gcm2 expression domain, however, is in debate, as both an endodermal and ectodermal expression has been reported [ 11 , 26 ]. In amniotes Gcm2 domain is clearly endodermal, thus the issue of which tissue expresses Gcm2 is of particular importance if homology is to be assigned. Gcm2 is expressed in pharyngeal pouches of the teleost fish zebrafish and the small-spotted catshark Scyliorhinus canicula [ 11 , 26 , 27 ].
Its expression patterns indicate that the tetrapod parathyroid glands and the gills of fish are evolutionarily related structures, and that the parathyroid glands likely come into being as a result of the transformation of the gills during tetrapod evolution. Histologically, the parathyroid glands are bounded by a thin fibrous capsule that overlies a network of adipose tissue, blood vessels and glandular parenchyma Fig.
The parathyroid glands from a wide range of species exhibit similar morphologic features. A large number of ultrastructural studies of the normal parathyroid glands have been reported in mammals [ 4 - 6 , 19 ].
Light micrograph of the human parathyroid gland. The gland comprises dense cords of chief cells clustered around capillaries. The parathyroid chief cells are the major cell type of the parathyroid glands in healthy subjects. Chief cells play a central role in calcium homeostasis by sensing changes in extracellular calcium and releasing the appropriate amount of PTH to correct or maintain normal blood calcium levels.
Chief cells undergo morphologic changes corresponding to different stages of the secretory cycle [ 4 - 6 , 19 ]. Chief cells in an inactive stage of their secretory cycle are cuboidal and have uncomplicated interdigitations between adjacent cells. There are numerous experiments, such as sympathectomy, electrical stimulation of vagus nerve, ovariectomy, hypophysectomy, and injection of calcium, propranolol, melatonin, and streptozotocin, suppress chief cells to release PTH inactive stage.
Experiments such as low calcium diet, vagotomy, hypergravity environment, pinectomy, and injection of estrogen, isoproterenol, and calcitonin, stimulate chief cells to enter active stage [ 6 ]. The cytoplasm contains poorly developed organelles and infrequent secretory granules Fig. There are numerous lipid droplets, lysosomes or glycogen particles. Chief cells in the active stage are oval or polygonal in shape.
The plasma membranes of adjacent chief cells purse a tortuous course with complex interdigitations. The nuclei are oval or spherical with occasional invaginations. The cells have rich free ribosomes and the rough endoplasmic reticulum.
The Golgi complexes contain numerous prosecretory granules. The secretory granules of to nm in diameter are distributed around the Golgi complexes and peripheral cytoplasm. Some of them are situated close to the plasma membrane Fig. In the electron microscopic autoradiograph of the newt parathyroid gland after injection of 3 H-leucine, most silver grains are seen over the rough endoplasmic reticulum at 15 minutes, over the Golgi complexes at 30 minutes, and over secretory granules at 60 minutes [ 5 ].
Similar results have been reported in the rat parathyroid gland [ 6 ]. From these findings, the synthesis of secretory protein is related to ribosomes lining the rough endoplasmic reticulum, newly synthesized secretory protein is transferred from the endoplasmic reticulum to the Golgi complexes and secretory granule.
Immunocytochemical localization of PTH can be examined by using the protein A-gold technique. Protein A-gold particles are concentrated over the secretory granules and Golgi vacuoles [ 5 , 6 , 29 ]. No particles are detected over the rough endoplasmic reticulum. Rat parathyroid chief cells of the inactive stage A and active stage B. Inactive chief cells contain poorly developed Golgi complexes G and infrequent secretory granules. Well developed Golgi complexes G and numerous secretory granules arrowheads are found in the active chief cells.
Another cell type in the parathyroid glands of certain animal species and humans is the oxyphil cell [ 4 - 6 ]. These cells are absent from the parathyroid glands of the rat, chicken, and many species of lower animals. Oxyphil cells are observed either singly or in small groups interspersed between chief cells.
They are larger than chief cells and the abundant cytoplasm is filled with numerous large mitochondria Fig. Mitochondria are also the site for vitamin D metabolism. The rough endoplasmic reticulum is scarce and the Golgi complex associated with few prosecretory granules is poorly developed. A few secretory granules, lysosomes, lipid droplets and glycogen particles are present.
Oxyphil cells have been shown histochemically to have a higher oxidative and hydrolytic enzyme activity than chief cells associated with the marked increase in mitochondria. Transitional oxyphil cells between the chief cells and oxyphil cells are observed in the parathyroid gland [ 5 , 6 , 31 ].
Both transitional and oxyphil cells are not altered in response to either short-term hypocalcemia or hypercalcemia in animals, but they may be increased in response to long-term stimulation of human parathyroid glands. It has been shown that the number of oxyphil cells increases with aging and some metabolic deragements.
The cell increases dramatically in number especially in patients with chronic kidney disease [ 32 ].
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