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calcitonin-related polypeptide alpha OKDB#: 313
 Symbols: CALCA Species: human
 Synonyms: CT, KC, CGRP, CALC1, CGRP1, CGRP-I  Locus: 11p15.2 in Homo sapiens


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General Comment Calcitonin is a peptide hormone synthesized by the parafollicular cells of the thyroid. It causes reduction in serum calcium - an effect opposite to that of parathyroid hormone. Human calcitonin contains 32 amino acids and has a molecular weight of 3,421. Jacobs et al. (1981) found that multiple calcitonin polypeptides are encoded in a single messenger RNA. Rosenfeld et al. (1982) presented evidence that alternative RNA splicing of the transcripts of the calcitonin gene is responsible for the production of different polypeptide products. Cacitonin gene related peptide is a 21-amino acid peptide that flanks calcitonin on its C-terminal side. Its concentration is higher in males than in females and approximately the same as calcitonin. Hillyard et al. (1983) showed that like calcitonin, CGRP may be involved in both plasma calcium regulation and skeletal maintenance.

NCBI Summary: This gene encodes the peptide hormones calcitonin, calcitonin gene-related peptide and katacalcin by tissue-specific alternative RNA splicing of the gene transcripts and cleavage of inactive precursor proteins. Calcitonin is involved in calcium regulation and acts to regulate phosphorus metabolism. Calcitonin gene-related peptide functions as a vasodilator and as an antimicrobial peptide while katacalcin is a calcium-lowering peptide. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2014]
General function Ligand, Hormone
Comment Calcitonin gene related peptide is a peptide hormone synthesized by the parafollicular cells of the thyroid.
Cellular localization
Comment Serum calcitonin gene-related peptide levels in women with polycystic ovary syndrome. Fenkci SM et al. PURPOSE: Calcitonin gene-related peptide (CGRP) is an amino acid neuropeptide with widespread expression. It has potent effects on lipid and energy metabolism. It induces insulin resistance. This study was planned to determine CGRP levels in women with polycystic ovary syndrome (PCOS). METHODS: Forty-seven women with PCOS and 34 healthy controls were evaluated in this controlled clinical study. Serum lipid sub-fractions, postprandial and fasting glucose, insulin and other hormones (gonadotropins, androgens) and CGRP levels were measured. Homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. RESULTS: Waist measurements, postprandial and fasting glucose and fasting insulin levels and free androgen index and HOMA-IR were significantly higher in subjects with PCOS. However, the women with PCOS had considerably lower high-density lipoprotein cholesterol levels than healthy subjects. Serum CGRP levels were higher in study subjects than in controls, although it was statistically insignificant. CONCLUSIONS: Serum CGRP level was not related with insulin resistance, ovarian hyperandrogenism and dyslipidemia in abdominally obese women with PCOS. These outcomes propose that CGRP may not play a pivotal role in the pathogenesis of PCOS. Plasma level of calcitonin gene-related peptide in patients with polycystic ovary syndrome and its relationship to hormonal and metabolic parameters. Zhang Z et al. The aim of the study was to evaluate the plasma level of calcitonin gene-related peptide (CGRP) in patients with polycystic ovary syndrome (PCOS) and its relationship to hormonal and metabolic parameters. We also observed the effect of CGRP on testosterone (T) and estradiol (E(2)) release in cultured human granulosa cells. PCOS subjects (n=215) and matched healthy control women (n=103) at age of 22-38 years were enrolled in this study. We analyzed plasma CGRP concentrations, relationship of plasma CGRP with insulin resistance (IR), body mass index (BMI), luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio and T. The T and E(2) release levels of cultured human granulosa cells treated by CGRP were also measured. The results showed that plasma CGRP concentrations were significantly higher in women with PCOS than those of control subjects. In women with PCOS, there was a strong positive correlation between the plasma CGRP level with HOMA-IR, AUC-insulin, AUC-glucose, the ratio of LH/FSH and plasma T concentration. Human granulosa cells expressed CGRP receptor. Exogenous CGRP caused an elevation of T and E(2) released from the human granulosa cells. These findings suggest that CGRP may participate in the pathophysiological process of PCOS.
Ovarian function Steroid metabolism, Luteinization, Oocyte maturation
Comment Effect of calcitonin gene-related peptide on the maturation of oocyte in vitro]. [Zhang Z et al. Objective: To explore the effect of calcitonin gene-related peptide (CGRP) on murine oocyte maturation. Methods: After injection of pregnant mare serum gonadotropin (PMSG, 10 U, i.p.) for 48 h, 6-week old female Kunming mice were killed, and the cumulus oocyte complexes (COCs) were collected from ovaries and inoculated in the culture plate by 30-40/hole. The COCs were treated with 4 concentrations of CGRP (0, 10(-10), 10(-9), and 10(-8) mol/L), and the germinal vesicle breakdown (GVBD) and polar body I (PBI) were examined. Human granulosa cells were also cultured with CGRP (0, 10(-10), 10(-9), 10(-8) mol/L) and levels of intracellular cyclic adenosine monophosphate (cAMP) were measured. Results: Exogenous CGRP caused a decrease in GVBD and PBI in COCs, and an increase in cAMP levels in human granulosa cells in a concentration-dependent manner. Conclusion: CGRP can inhibit the oocyte maturation, which may be related to the increased content of cAMP in granulosa cells. Majewski et al. (1996) showed that calcitonin gene realted peptide is in some afferent neurons innervating the porcine ovary. The ovarian artery as well as arteries of the paraovarian plexus were moderately supplied with CGRP nerve fibres. Additional fibers can be found occassionally in the interstitial tissue and in the vicinity of ovarian follicles. CGPR containing nerves enter the ovary via the plexus nerve and are probably involved in the regulation of vasomotor function. Tsai SC, et al. (Am J Physiol. 1999) demonstrated that salmon calcitonin (sCT) inhibits progesterone production in rats by preventing the stimulatory effect of GnRH on LH release in rat APs and acting directly on ovarian granulosa cells to decrease the activities of post-cAMP pathway and steroidogenic enzymes.
Expression regulated by
Comment
Ovarian localization
Comment
Follicle stages
Comment The distribution and influence of calcitonin gene-related peptide (CGRP) on the perfusion pressure in the isolated ovarian artery in the pig. Markiewicz W,et al . A moderate number of delicate CGRP-immunoreactive (CGRP-IR) varicose nerve terminals were found at the adventitia-media border of the sexually mature porcine ovarian artery by means of a routine single immunolabelling technique. Additionally, a pharmacological analysis was performed of the function fulfilled by alpha-CGRP and its C-terminal fragment (Tyr27) alpha-CGRP(27-37) in the porcine isolated ovarian artery, collected on days 8-13 of the oestrous cycle. It was shown that alpha-CGRP (10(-8) M) caused a decrease in the perfusion pressure of the porcine isolated ovarian artery of 16% (p < 0.05), while (Tyr27) alpha-CGRP(27-37), added at the same concentration, reduced perfusion pressure by 13% (p > 0.05). Thus, we concluded that alpha-CGRP released from perivascular terminals may cause relaxation of the ovarian artery and, furthermore, that the potency of this action is dependent on the length of the chain of this peptide produced during the deactivation of the molecule by tissue proteases.
Phenotypes PCO (polycystic ovarian syndrome)
Mutations 1 mutations

Species: human
Mutation name: None
type: None
fertility: None
Comment: Alevizaki et al. (1989) found a 1-bp (T) insertion in the calcitonin gene in a young male patient with osteoporosis. The patient had no detectable plasma concentrations of calcitonin and had responded well to calcitonin replacement treatment for 9 years. Genomic Southern blots with various restriction enzymes showed no large abnormalities in his calcitonin gene. The extra nucleotide was inserted at position 462 in the intron separating exons 4 and 5. The extra base was contiguous to a CTGAC sequence that is the consensus sequence for formation of a branch point during splicing, as shown by a similar intronic sequence in the beta-globin gene. Presumably the mutation interferes with the splice that leads to production of CGRP.

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created: Dec. 7, 1999, midnight by: Sung   email:
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last update: Jan. 11, 2016, 3:17 p.m. by: hsueh    email:



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