Tags

Type your tag names separated by a space and hit enter

Thymus-associated parathyroid hormone has two cellular origins with distinct endocrine and immunological functions.
PLoS Genet 2010; 6(12):e1001251PG

Abstract

In mammals, parathyroid hormone (PTH) is a key regulator of extracellular calcium and inorganic phosphorus homeostasis. Although the parathyroid glands were thought to be the only source of PTH, extra-parathyroid PTH production in the thymus, which shares a common origin with parathyroids during organogenesis, has been proposed to provide an auxiliary source of PTH, resulting in a higher than expected survival rate for aparathyroid Gcm2⁻/⁻ mutants. However, the developmental ontogeny and cellular identity of these "thymic" PTH-expressing cells is unknown. We found that the lethality of aparathyroid Gcm2⁻/⁻ mutants was affected by genetic background without relation to serum PTH levels, suggesting a need to reconsider the physiological function of thymic PTH. We identified two sources of extra-parathyroid PTH in wild-type mice. Incomplete separation of the parathyroid and thymus organs during organogenesis resulted in misplaced, isolated parathyroid cells that were often attached to the thymus; this was the major source of thymic PTH in normal mice. Analysis of thymus and parathyroid organogenesis in human embryos showed a broadly similar result, indicating that these results may provide insight into human parathyroid development. In addition, medullary thymic epithelial cells (mTECs) express PTH in a Gcm2-independent manner that requires TEC differentiation and is consistent with expression as a self-antigen for negative selection. Genetic or surgical removal of the thymus indicated that thymus-derived PTH in Gcm2⁻/⁻ mutants did not provide auxiliary endocrine function. Our data show conclusively that the thymus does not serve as an auxiliary source of either serum PTH or parathyroid function. We further show that the normal process of parathyroid organogenesis in both mice and humans leads to the generation of multiple small parathyroid clusters in addition to the main parathyroid glands, that are the likely source of physiologically relevant "thymic PTH."

Authors+Show Affiliations

Department of Genetics, University of Georgia, Athens, Georgia, United States of America.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21203493

Citation

Liu, Zhijie, et al. "Thymus-associated Parathyroid Hormone Has Two Cellular Origins With Distinct Endocrine and Immunological Functions." PLoS Genetics, vol. 6, no. 12, 2010, pp. e1001251.
Liu Z, Farley A, Chen L, et al. Thymus-associated parathyroid hormone has two cellular origins with distinct endocrine and immunological functions. PLoS Genet. 2010;6(12):e1001251.
Liu, Z., Farley, A., Chen, L., Kirby, B. J., Kovacs, C. S., Blackburn, C. C., & Manley, N. R. (2010). Thymus-associated parathyroid hormone has two cellular origins with distinct endocrine and immunological functions. PLoS Genetics, 6(12), pp. e1001251. doi:10.1371/journal.pgen.1001251.
Liu Z, et al. Thymus-associated Parathyroid Hormone Has Two Cellular Origins With Distinct Endocrine and Immunological Functions. PLoS Genet. 2010 Dec 23;6(12):e1001251. PubMed PMID: 21203493.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thymus-associated parathyroid hormone has two cellular origins with distinct endocrine and immunological functions. AU - Liu,Zhijie, AU - Farley,Alison, AU - Chen,Lizhen, AU - Kirby,Beth J, AU - Kovacs,Christopher S, AU - Blackburn,C Clare, AU - Manley,Nancy R, Y1 - 2010/12/23/ PY - 2010/09/13/received PY - 2010/11/17/accepted PY - 2011/1/5/entrez PY - 2011/1/5/pubmed PY - 2011/3/29/medline SP - e1001251 EP - e1001251 JF - PLoS genetics JO - PLoS Genet. VL - 6 IS - 12 N2 - In mammals, parathyroid hormone (PTH) is a key regulator of extracellular calcium and inorganic phosphorus homeostasis. Although the parathyroid glands were thought to be the only source of PTH, extra-parathyroid PTH production in the thymus, which shares a common origin with parathyroids during organogenesis, has been proposed to provide an auxiliary source of PTH, resulting in a higher than expected survival rate for aparathyroid Gcm2⁻/⁻ mutants. However, the developmental ontogeny and cellular identity of these "thymic" PTH-expressing cells is unknown. We found that the lethality of aparathyroid Gcm2⁻/⁻ mutants was affected by genetic background without relation to serum PTH levels, suggesting a need to reconsider the physiological function of thymic PTH. We identified two sources of extra-parathyroid PTH in wild-type mice. Incomplete separation of the parathyroid and thymus organs during organogenesis resulted in misplaced, isolated parathyroid cells that were often attached to the thymus; this was the major source of thymic PTH in normal mice. Analysis of thymus and parathyroid organogenesis in human embryos showed a broadly similar result, indicating that these results may provide insight into human parathyroid development. In addition, medullary thymic epithelial cells (mTECs) express PTH in a Gcm2-independent manner that requires TEC differentiation and is consistent with expression as a self-antigen for negative selection. Genetic or surgical removal of the thymus indicated that thymus-derived PTH in Gcm2⁻/⁻ mutants did not provide auxiliary endocrine function. Our data show conclusively that the thymus does not serve as an auxiliary source of either serum PTH or parathyroid function. We further show that the normal process of parathyroid organogenesis in both mice and humans leads to the generation of multiple small parathyroid clusters in addition to the main parathyroid glands, that are the likely source of physiologically relevant "thymic PTH." SN - 1553-7404 UR - https://www.unboundmedicine.com/medline/citation/21203493/Thymus_associated_parathyroid_hormone_has_two_cellular_origins_with_distinct_endocrine_and_immunological_functions_ L2 - http://dx.plos.org/10.1371/journal.pgen.1001251 DB - PRIME DP - Unbound Medicine ER -