However, in studies in children with congenital hypothyroidism and in thyroidectomized patients, bone loss has been attributed to inadequate thyroid replacement and not to the absence of CT [ 24 , 57 ]. Also, skeletal changes have not been observed in patients with elevated CT values in medullary thyroid carcinoma [ 31 ]. Potentially, there may be different challenges among species in defending against hypercalcemia. CT is an older hormone phylogenetically than PTH dating back to fish in the ocean with a need to protect against hypercalcemia while PTH developed in land-dwelling animals to protect against hypocalcemia.
As such, this may be an explanation why salmon CT is more potent than CT from mammals [ 7 , 58 ]. Not often discussed is that the need to protect against hypercalcemia may be different among land-dwelling animals. Humans and domesticated animals eat meals on a regular basis throughout the day. Conversely, carnivorous animals in the wild eat large meals consisting of a high percent of their body mass at irregular intervals.
Besides a large protein load, the ingestion of calcium and phosphate is also great. Serum calcium did not change, but serum phosphorus increased from 6. Serum bicarbonate increased from 11 mM fasting to 20 mM and remained significantly elevated for 6 days. Blood pH which was 7. Whether similar physiologic adaptations occur in infrequently feeding carnivorous mammals in the wild and whether CT secretion plays a role and is possibly stimulated by gastrin secretion or the calcium load is an interesting question.
Also, the possibility exists that post-prandial alkalemia could be an additional stimulus for CT secretion. Gender and age differences in serum CT values have been reported. Deftos and associates reported that in normal adult subjects, basal CT values were similar between men and women, but basal CT values decreased with age in both groups and the response to a calcium or pentagastrin challenge was less in women than in men [ 25 , 60 ]. A subsequent study by another group showed lower basal and stimulated CT values in women than in men, but no decrement in CT values with age [ 9 ].
The CT difference between women and men has been ascribed to a lower CT secretion rate in women [ 9 ].
In post-menopausal women, estrogen administration may increase CT levels [ 61 ]. Finally, infants and children may have higher serum CT levels than adults [ 62 , 63 ]. Serum CT and 1,25D values are increased during pregnancy and lactation [ 16 , 17 , 64 ].
Interestingly, CT has been shown to stimulate 1,25D production in the kidney in the proximal straight tubule while PTH and phosphorus stimulate 1,25D production in the proximal convoluted tubule [ 12 , 13 ]. Similar changes are seen in mice and rats during lactation and weaning [ 18 ]. Administration of salmon CT in the null mice prevented the differences between null and wild-type mice. While CT is known to inhibit osteoclast activity [ 19 , 65 ], the identification of CT receptors on osteocytes suggests that CT may also modify osteocyte function [ 31 ].
In summary, CT may have an important functional role in pregnancy and lactation. Since the discovery of CT in the early s, much interest has been focused on whether CT has an important role in normal bone health. It has been postulated that CT acts postprandially to use phosphate to store calcium in bone [ 21 , 66 ]. But except perhaps for pregnancy and lactation, no specific CT deficiency or excess bone syndromes have been identified [ 66 ].
CT has been used to treat post-menopausal osteoporosis [ 67 ], but its benefit has not been dramatic. At least in ovariectomized and in normal beagle dogs in which bone histomorphometry and physical bone strength were evaluated, CT administration decreased osteoblast function, bone formation and physical bone strength [ 68 , 69 ].
However, in a knockout mouse model in which the CT gene was deleted, no developmental defects were observed and procreation was normal [ 70 ]. Moreover, bone findings included an increase in trabecular bone volume and bone formation at 1 and 3 months of age while bone resorption was not changed.
Baseline serum calcium values were unaffected but the administration of PTH resulted in greater hypercalcemia and urine deoxypyridinoline crosslinks excretion than in wild-type mice. Interestingly, the CT female knockout mouse appeared to be protected against ovariectomy-induced bone loss. While the effect of CT administration to treat hypercalcemia has been attributed to its inhibition of osteoclasts [ 19 ], an escape of osteoclasts from the effects of prolonged CT administration is well known [ 20 , 71 ].
This result could possibly explain the failure to observe increased bone resorption in the absence of CT. The enhanced bone formation observed in the absence of CT is perhaps more difficult to explain. But CT has been shown to modify cell cultures of osteoblasts and osteocytes [ 72 ].
One intriguing hypothesis based on the finding of CT receptors on osteocytes, is that CT could potentially modify osteocyte products such as FGF23 or perhaps more importantly, sclerostin, a known regulator of bone formation [ 31 ].
The kidney is the primary site for metabolism of CT [ 8 , 10 ]. As might be expected with decreased metabolism of CT in renal failure, CT values are increased in azotemic humans and animals [ 32 , 34 , 73 , 74 ].
As in normal humans and animals, a sigmoidal CT response is seen during the induction of hypercalcemia in azotemic humans and animals [ 32 — 34 ]. The CT response to hypercalcemia has been shown to protect against the development of acute hypercalcemia in azotemic rats [ 11 ]. Also, a normal stimulatory response to pentagastrin has been reported in patients with chronic renal failure [ 74 ].
In a bone histomorphometric study, no correlation was found between bone activity and CT levels while correlations were observed with PTH [ 75 ].
Finally, several studies from many years ago showed that treatment with CT failed to improve renal osteodystrophy [ 76 — 78 ]. Strong evidence exists that the calcitonin response to an increase in the serum calcium concentration protects against the development of acute hypercalcemia.
Unlike other hormones, no specific developmental or metabolic abnormalities have been associated with a deficiency or excess of calcitonin except for diarrhea in a few patients with medullary thyroid carcinoma. Unlike other hormones except for gender-specific hormones such as estrogen and androgens, distinct differences in the characteristics of calcitonin secretion appear to be present between males and females.
Like the PTH response to hypocalcemia, the calcitonin response to hypercalcemia is a sigmoidal curve. Unlike PTH for which virtually all humans and animals respond to hypocalcemia with a PTH response, a number of humans and animals fail to produce a calcitonin response to hypercalcemia.
Unlike PTH which only seems to respond to calcium perhaps modified by pH, calcitonin, besides responding to calcium, also responds to gastrointestinal hormones of which gastrin has been the best studied. The postprandial increase in gastrin and its association with calcitonin secretion has led to the hypothesis that calcitonin may have an important postprandial role in facilitating calcium and phosphate deposition in bone.
Despite interest in this concept, no definite proof has been established. However, renewed interest in calcitonin may develop because of potential effects of calcitonin on the osteocyte, but bone abnormalities resulting from a deficiency or excess have not been shown so that any effect must be subtle or counterbalanced by other factors. Recent studies in the calcitonin gene knockout mouse model, have suggested that the absence of calcitonin increased bone mass through enhanced bone formation without having an effect on bone resorption which might have been predicted based on previous known effects of calcitonin on the osteoclast.
Finally, whether increased calcitonin levels have any role in chronic kidney disease remains unknown. A summary of the known or possible effects or responses of calcitonin is shown in the Table 1. In conclusion, calcitonin, which is no longer even included as a chapter in the most recent edition of the ASBMR Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism [ 79 ], is a hormone preserved during evolution from ocean to land-based animals that continues to be an enigma more than 50 years after its discovery.
None of the authors have any conflicts of interest. The content of this review has not been published previously. National Center for Biotechnology Information , U. Journal List Clin Kidney J v. Clin Kidney J. Published online Mar Arnold J.
Felsenfeld and Barton S. Author information Article notes Copyright and License information Disclaimer. Correspondence to: Arnold Felsenfeld; E-mail: ude. Received Jan 3; Accepted Jan For commercial re-use, please contact journals. This article has been cited by other articles in PMC. Abstract Calcitonin is a 32 amino acid hormone secreted by the C-cells of the thyroid gland. There does not seem to be any direct deleterious effect on the body as a result of having too much calcitonin.
Medullary thyroid cancer is a rare type of cancer that arises from the C-cells in the thyroid gland that secrete calcitonin. It is sometimes associated with multiple endocrine neoplasia type 2a and multiple endocrine neoplasia type 2b.
Patients with medullary thyroid cancer have high calcitonin levels in their bloodstream. However, it is important to note that these high calcitonin levels are a consequence of this condition, not a direct causal factor. There does not seem to be any clinical effect on the body as a result of having too little calcitonin. Patients who have had their thyroid gland removed, and have undetectable levels of calcitonin in their blood, show no adverse symptoms or signs as a result of this.
About Contact Events News. Search Search. You and Your Hormones. It contains a single disulfide bond, which causes the amino terminus to assume the shape of a ring. Alternative splicing of the calcitonin pre-mRNA can yield a mRNA encoding calcitonin gene-related peptide; that peptide appears to function in the nervous and vascular systems. The calcitonin receptor has been cloned and shown to be a member of the seven-transmembrane, G protein-coupled receptor family.
A large and diverse set of effects has been attributed to calcitonin, but in many cases, these were seen in response to pharmacologic doses of the hormone, and their physiologic relevance is suspect. It seems clear however, that calcitonin plays a role in calcium and phosphorus metabolism.
In particular, calcitonin has the ability to decrease blood calcium levels at least in part by effects on two well-studied target organs:. Facebook-f Twitter Instagram Youtube. Calculate Your Risk. Related Articles. Cancer Survivors March 20, What Is Secondary Prevention of Osteoporosis? July 21, Understanding Bone Density Results January 13, American Bone Health and Susan G. Cancer and Bone Health February 26,
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