Skip to main content
SpringerLink
Log in

Role of intron 5 C/T polymorphism of the calcium sensing receptor gene in the regulation of the serum FSH and LH in post-menopausal women

  • Original Articles
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Objective: High extracellular calcium concentration (Cao 2+) acts to inhibit calcium sensing receptor (CaR) signalling on cellular surfaces in parathyroid glands. This receptor is, however, also expressed on the membranes of some non-calciotropic endocrine cells, including pituitary-derived cells. The aim of our study was to analyse relationships between the CaR gene and the circulating FSH and LH in normal postmenopausal women. Methods: A total of 95 untreated euparathyroid post-menopausal women were investigated in the study. The serum FSH and LH levels were evaluated in relationship to allele combinations of the CaR gene (C/T polymorphism in the intron 5 and A986S polymorphism in exon 7), using an analysis of co-variance (ANCOVA) model. Results: Distribution of TT, TC and CC allele combinations (intron 5 C/T polymorphism) was 51, 43 and 6 %, respectively. Higher serum FSH and LH levels were found in carriers of C allele than in women without this allele (p<0.002 and p<0.03, respectively). No correlations were found between A986S polymorphism and serum FSH and LH levels. Conclusions: Serum FSH and LH levels are associated with intron 5 C/T (but not A986S) polymorphism of the CaR gene in untreated post-menopausal women. The physiological role of the CaR gene in the regulation of the gonadotropic function needs to be further investigated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Brown EM, MacLeod RJ. Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev 2001, 81: 239–97.

    CAS  PubMed  Google Scholar 

  2. Emanuel LR, Adler GK, Kifor O, et al. Calcium-sensing receptor expression and regulation by extracellular calcium in the At-T20 pituitary cell line. Mol Endocrinol 1996, 10: 555–65.

    CAS  PubMed  Google Scholar 

  3. Cole DE, Peltekova VD, Rubin LA, et al. A986S polymorphism of the calcium-sensing receptor gene and circulating calcium concentrations. Lancet 1999, 353: 112–5.

    Article  CAS  PubMed  Google Scholar 

  4. Miedlich S, Lamesch P, Mueller A, Paschke R. Frequency of the calcium-sensing receptor variant A986S in patients with primary hyperparathyroidism. Eur J Endocrinol 2001, 145: 421–7.

    Article  CAS  PubMed  Google Scholar 

  5. Cetani F, Borsari S, Vignali E, et al. Calcium -sensing receptor gene polymorphisms in primary hyperparathyroidism. J Endocrinol Invest 2002, 25: 614–9.

    Article  CAS  PubMed  Google Scholar 

  6. Koishi S, Aida K, Tawata M, Onaya T. Polymorphism of the human Ca(2+) — sensing receptor gene in Japanese individuals: no relation to non-insulin dependent diabetes mellitus. Horm Metab Res 1996, 28: 541–4.

    Article  CAS  PubMed  Google Scholar 

  7. Järvinen TL, Kannus P, Sievänen H. Estrogen and bone — a reproductive and locomotive perspective. J Bone Miner Res 2003, 18: 1921–31.

    Article  PubMed  Google Scholar 

  8. Zofkova I, Hill M, Zajickova K. Dehydroepiandrosterone status in postmenopausal women is determined by the gene for the vitamin D receptor. Horm Metab Res 2002, 34: 127–31.

    Article  CAS  PubMed  Google Scholar 

  9. Zofkova I, Zajickova K, Hill M. Postmenopausal serum androstenedione levels are associated with the calcitonin receptor gene polymorphism T1377C. A pilot study. J Endocrinol Invest 2004, 27: 442–4.

    Article  CAS  PubMed  Google Scholar 

  10. Malmed S, Kleinberg D. Anterior pituitary. Development, anatomy and overview of control of hormone secretion. In: PR Larsen, HM Kronenberg, S Melmed, KS Polansky eds. Williams Textbook of Endocrinology. Elsevier Science (USA). 2002, 177–81.

    Google Scholar 

  11. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucl Acids Res 1988, 16: 1215–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Yano S, Sugimoto T, Kanzawa M, et al. Association of polymorphic alleles of the calcium-sensing receptor gene with parathyroid hormone secretion in hemodialysis patients. Nephron 2000, 85: 317–23.

    Article  CAS  PubMed  Google Scholar 

  13. Lorentzon M, Lorentzon R, Lerner UH, Nordström P. Calcium sensing receptor gene polymorphism, circulating calcium concentrations and bone mineral density in healthy adolescent girls. Eur J Endocrinol 2001, 144: 257–61.

    Article  CAS  PubMed  Google Scholar 

  14. Nissenson RA. Parathyroid hormone. Biosynthesis, secretion, and chemistry of PTH. In: HL Henry, AW Norman eds. Encyclopedia of Hormones. ed 3th. San Diego: Academic Press, An imprint of Elsevier Inc. 2003, 146–153.

    Chapter  Google Scholar 

  15. Bai M, Quinn S, Trivedi S, et al. Expression and characterization of inactivating and activating mutations in the human Cao 2+ — sensing receptor. J Biol Chem 1998, 271: 19537–45.

    Google Scholar 

  16. Yamauchi M, Sugimoto T, Yamaguchi T, et al. Association of polymorphic alleles of the calcium-sensing receptor gene with the clinical severity of primary hyperparathyroidism. Clin Endocrinol (Oxf) 2001, 55: 373–9.

    Article  CAS  Google Scholar 

  17. Shorte SL, Schofield JG. The effect of extracellular polyvalent cations on bovine anterior pituitary cells. Evidence for a Ca2+-sensing receptor coupled to release of intracellular calcium stores. Cell Calcium 1996, 19: 43–57.

    Article  CAS  PubMed  Google Scholar 

  18. Emanuel RL, Adler GK, Kifor O, et al. Calcium-sensing receptor expression and regulation by extracellular calcium in the AtT-20 pituitary cell line. Mol Endocrinol 1996, 64: 555–65.

    Google Scholar 

  19. Ferry S, Chatel B, Dodd RH, et al. Effects of divalent cations and of a calcimimetic on adrenocorticotropic hormone release in pituitary tumor cells. Biochem Biophys Res Commun 1997, 238: 866–73.

    Article  CAS  PubMed  Google Scholar 

  20. Veldhuis JD, Borgis JL, Drake CR, Rogol AD. Divergent influences of calcium ions on releasing factor-stimulated anterior pituitary hormone secretion in normal man. J Clin Endocrinol Metab 1984, 59: 56–61.

    Article  CAS  PubMed  Google Scholar 

  21. Bates MD, Conn PM. Calcium mobilization in the pituitary gonadotrope: relative roles of intra- and extracellular sources. Endocrinology 1984, 115: 1380–5.

    Article  CAS  PubMed  Google Scholar 

  22. Sedej S, Tsujimoto T, Zorec R, Rupnik M. Voltage-activated Ca2+ channels and their role in the endocrine function of the pituitary gland in newborn and adult mice. J Physiol 2004, 555: 769–82.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Cetani F, Pardi E, Borsari S, et al. Calcium-sensing receptor gene polymorphism is not associated with bone mineral density in Italian postmenopausal women. Eur J Endocrinology 2003, 148: 603–7.

    Article  CAS  Google Scholar 

  24. Rubin LA, Peltekova V, Janicic N, et al. Calcium sensing receptor gene: analysis of polymorphism frequency. Scand J Clin Lab Invest 1997, 57: 122–5.

    Article  CAS  Google Scholar 

  25. Takacs I, Speer G, Bajnok E, et al. Lack of association between calcium-sensing receptor gene “A896S” polymorphism and Hungarian postmenopausal bone mineral density in women. Bone 2002, 30: 849–52.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Endocrinology, Narodnf 8, 116 94, Prague 1, Czech Republic

    I. Žofková MD, PhD, DSc, K. Zajícková, M. Hill & M. Vanková

Authors
  1. I. Žofková MD, PhD, DSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Zajícková
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Hill
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Vanková
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. Žofková MD, PhD, DSc.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Žofková, I., Zajícková, K., Hill, M. et al. Role of intron 5 C/T polymorphism of the calcium sensing receptor gene in the regulation of the serum FSH and LH in post-menopausal women. J Endocrinol Invest 28, 638–642 (2005). https://doi.org/10.1007/BF03347263

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03347263

Key-words

Search

Navigation