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. 1975 Jan;55(1):201–204. doi: 10.1172/JCI107913

Direct evidence of estrogen modulation of pituitary sensitivity to luteinizing hormone-releasing factor during the menstrual cycle.

C F Wang, S S Yen
PMCID: PMC301734  PMID: 1088908

Abstract

To delineate the role of estradiol in the augmented pituitary gonadotropin responsiveness to synthetic luteinizing hormone releasing factor (LRF) seen during high-estrogen phases of the ovulatory cycles (late follicular and midluteal phases), the anti-estrogenic effect of clomiphene citrate (Clomid) on pituitary response to LRF was evaluated during different phases of the ovulatory cycle. Clomid administration (100 mg/day times 5 days) completely negates the augmented gonadotropin responses to LRF (150 mug) during late follicular and midluteal phases observed during the control studies. Thus, a quantitatively and qualitatively similar pituitary sensitivity to LRF during three distinct phases of the menstrual cycle was induced by Clomid treatment that resembles the LRF responsiveness of themale pituitary. The present study demonstrates the pituitary component of the estrogen-induced changes in the sensitivity to LRF. From this and previous data, we conclude that the increases of estradiol secretion associated with the follicular maturation and corpus luteum formation represent a major component of the feedback signal in the modulation of cyclic gonadotropin release occasioned in a large measure by the augmented pituitary sensitivity to LRF.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arimura A., Kastin A. J., Schally A. V., Saito M., Kumasaka T., Yaoi Y., Nishi N., Okura K. Immunoreactive LH-releasing hormone in plasma: midcycle elevation in women. J Clin Endocrinol Metab. 1974 Mar;38(3):510–513. doi: 10.1210/jcem-38-3-510. [DOI] [PubMed] [Google Scholar]
  2. BOGDANOVE E. M. DIRECT GONAD-PITUITARY FEEDBACK: AN ANALYSIS OF EFFECTS OF INTRACRANIAL ESTROGENIC DEPOTS ON GONADOTROPHIN SECRETION. Endocrinology. 1963 Dec;73:696–712. doi: 10.1210/endo-73-6-696. [DOI] [PubMed] [Google Scholar]
  3. Debeljuk L., Vilchez-Martinez J. A., Arimura A., Schally A. V. Effect of gonadal steroids on the response to LH-RH in intact and castrated male rats. Endocrinology. 1974 Jun;94(6):1519–1524. doi: 10.1210/endo-94-6-1519. [DOI] [PubMed] [Google Scholar]
  4. Igarashi M., Ibuki Y., Kubo H., Kamioka J., Yokota N., Ebara Y., Matsumoto S. Mode and site of action of clomiphene. Am J Obstet Gynecol. 1967 Jan 1;97(1):120–123. doi: 10.1016/0002-9378(67)90604-7. [DOI] [PubMed] [Google Scholar]
  5. Kato J., Kobayashi T., Villec C. A. Effect of clomiphene on the uptake of estradiol by the anterior hypothalamus and hypophysis. Endocrinology. 1968 May;82(5):1049–1052. doi: 10.1210/endo-82-5-1049. [DOI] [PubMed] [Google Scholar]
  6. Keye W. R., Jr, Jaffe R. B. Modulation of pituitary gonadotropin response to gonadotropin-releasing hormone by estradiol. J Clin Endocrinol Metab. 1974 May;38(5):805–810. doi: 10.1210/jcem-38-5-805. [DOI] [PubMed] [Google Scholar]
  7. Korach K. S., Muldoon T. G. Studies on the nature of the hypothalamic estradiol-concentrating mechanism in the male and female rat. Endocrinology. 1974 Mar;94(3):785–793. doi: 10.1210/endo-94-3-785. [DOI] [PubMed] [Google Scholar]
  8. Libertun C., Orias R., McCann S. M. Biphasic effect of estrogen on the sensitivity of the pituitary to luteinizing hormone-releasing factor (LRF). Endocrinology. 1974 Apr;94(4):1094–1100. doi: 10.1210/endo-94-4-1094. [DOI] [PubMed] [Google Scholar]
  9. Malacara J. M., Seyler Le J., Reichlin S. Luteinizing hormone releasing factor activity in peripheral blood from women during the midcycle luteinizing hormone ovulatory surge. J Clin Endocrinol. 1972;34:271–278. [PubMed] [Google Scholar]
  10. Maurer R., Woolley D. Distribution of 3H-estradiol in clomiphene-treated and neonatally androgenized rats. Endocrinology. 1971 Jun;88(6):1281–1287. doi: 10.1210/endo-88-6-1281. [DOI] [PubMed] [Google Scholar]
  11. Nillius S. J., Wide L. Variation in LH and FSH response to LH-releasing hormone during the menstrual cycle. J Obstet Gynaecol Br Commonw. 1972 Oct;79(10):865–873. doi: 10.1111/j.1471-0528.1972.tb12182.x. [DOI] [PubMed] [Google Scholar]
  12. ROY S., MAHESH V. B., GREENBLATT R. B. EFFECTS OF CLOMIPHENE ON THE PHYSIOLOGY OF REPRODUCTION IN THE RAT. 3. INHIBITION OF UPTAKE OF RADIOACTIVE OESTRADIOL BY THE UTERUS AND THE PITUITARY GLAND OF IMMATURE RAT. Acta Endocrinol (Copenh) 1964 Dec;47:669–675. [PubMed] [Google Scholar]
  13. Siler T. M., Yen S. S. Augmented gonadotropin response to synthetic LRF in hypogonadal state. J Clin Endocrinol Metab. 1973 Sep;37(3):491–494. doi: 10.1210/jcem-37-3-491. [DOI] [PubMed] [Google Scholar]
  14. Thompson I. E., Arfania J., Taymor M. L. Effects of estrogen and progesterone on pituitary response to stimulation by luteinizing hormone-releasing factor. J Clin Endocrinol Metab. 1973 Jul;37(1):152–155. doi: 10.1210/jcem-37-1-152. [DOI] [PubMed] [Google Scholar]
  15. Vandenberg G., DeVane G., Yen S. S. Effects of exogenous estrogen and progestin on pituitary responsiveness to synthetic luteinizing hormone-releasing factor. J Clin Invest. 1974 Jun;53(6):1750–1754. doi: 10.1172/JCI107727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Vandenberg G., Yen S. S. Effect of anti-estrogenic action of clomiphene during the menstrual cycle: evidence for a change in the feedback sensitivity. J Clin Endocrinol Metab. 1973 Sep;37(3):356–365. doi: 10.1210/jcem-37-3-356. [DOI] [PubMed] [Google Scholar]
  17. Yen S. C., Llerena L. A., Pearson O. H., Littell A. S. Disappearance rates of endogenous follicle-stimulating hormone in serum following surgical hypophysectomy in man. J Clin Endocrinol Metab. 1970 Mar;30(3):325–329. doi: 10.1210/jcem-30-3-325. [DOI] [PubMed] [Google Scholar]
  18. Yen S. S., Llerena O., Little B., Pearson O. H. Disappearance rates of endogenous luteinizing hormone and chorionic gonadotropin in man. J Clin Endocrinol Metab. 1968 Dec;28(12):1763–1767. doi: 10.1210/jcem-28-12-1763. [DOI] [PubMed] [Google Scholar]
  19. Yen S. S., VandenBerg G., Rebar R., Ehara Y. Variation of pituitary responsiveness to synthetic LRF during different phases of the menstrual cycle. J Clin Endocrinol Metab. 1972 Dec;35(6):931–934. doi: 10.1210/jcem-35-6-931. [DOI] [PubMed] [Google Scholar]
  20. Yen S. S., Vandenberg G., Siler T. M. Modulation of pituitary responsiveness to LRF by estrogen. J Clin Endocrinol Metab. 1974 Jul;39(1):170–177. doi: 10.1210/jcem-39-1-170. [DOI] [PubMed] [Google Scholar]

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