Letter | Published:

Sensitisation of pituitary cells to luteinising hormone releasing hormone by clomiphene citrate in vitro

Abstract

SINCE the original study of Greenblatt1 in 1962, clomiphene citrate (2 [P-(2-chloro-1, 2-diphenylvinyl) phenoxy] triethylamine dihydrogen citrate) (Clomid) has been used successfully to induce ovulation in anovulatory conditions. The ovulation inducing effect of Clomid is mediated through a transient increase in the pituitary release of luteinising hormone (LH) and follicle stimulating hormone (FSH), which in turn initiates follicular maturation and ovulation2,3. Although the mechanism of action of Clomid is unknown, this substance has been reported to possess both antioestrogenic and oestrogenic properties. Experimental studies of the pituitary, hypothalamus and uterus have shown that Clomid competitively inhibits oestradiol binding to oestrogen receptors, suggesting an antioestrogenic action4–7. On the other hand, the observation that Clomid stimulates uterine growth is suggestive of an oestrogenic action8,9. Oestradiol has been shown to increase the responsiveness of cultured pituitary cells to luteinising hormone releasing hormone (LHRH)10. We show here, using cultured pituitary cells as a model system, the possible antioestrogenic and oestrogenic effects of Clomid on LH release in vitro, and demonstrate that Clomid, like oestradiol-17β, increases the responsiveness of gonadotrophs to LHRH in vitro. We conclude that Clomid acts as an oestrogen rather than an antioestrogen on the pituitary gonadotrophs.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Greenblatt, R. B. Fert. Steril. 12, 402–404 (1962).

  2. 2

    Vandenberg, G. & Yen, S. S. C. J. clin. Endocrinol. Metab. 37, 356–365 (1973).

  3. 3

    Vaitukaitis, J. L., Bermudez, J. A., Cargille, C. M., Lippsett, M. B. & Ross, G. T. J. clin. Endocrinol. 32, 503–508 (1971).

  4. 4

    Kato, J., Kobayashi, T. & Ville, C. Endocrinology 82, 1049–1052 (1968).

  5. 5

    Kahwanago, I., Heinrichs, W. L. & Herrmann, W. L. Endocrinology 86, 1319–1326 (1970).

  6. 6

    Roy, S., Mahesh, V. B. & Greenblatt, R. B. Acta Endocrinol. 47, 669–675 (1970).

  7. 7

    Eisenfeld, A. J. & Axelrod, J. Biochem. Pharmac. 16, 1781–1785 (1967).

  8. 8

    Clark, J. H., Anderson, J. N. & Peck, E. J. Steroids 22, 707–718 (1973); Nature 251, 446–448 (1974).

  9. 9

    Terenius, L. & Ljungkvist, I. Gynec. Invest. 3, 96–107 (1972).

  10. 10

    Drouin, J., Lagace, L. & Labrie, F. Endocrinology 99, 1477–1481 (1976).

  11. 11

    Smith, O. W., Smith, G. V. & Kistner, R. W. J. Am. Med. Ass. 184, 878–886 (1963).

  12. 12

    Hammerstein, J. Acta Endocrinol., Suppl. 119, 79 (1967).

  13. 13

    Gunaga, K. P., Kawano, A. & Menon, K. M. J. Neuroendocrinology 16 273–281 (1974).

  14. 14

    Weissman, B. A., Daly, J. W. & Skolnick, P. Endocrinology 97, 1559–1566 (1975).

  15. 15

    Weissman, B. A. & Skolnick, P. Neuroendocrinology 18, 27–34 (1975).

  16. 16

    Vale, W., Grant, G., Amoss, M., Blackwell, R. & Guillemin, R. Endocrinology 91, 562–571 (1972).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.