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. 1987 Sep;80(3):631–638. doi: 10.1172/JCI113115

Estradiol modulates the pulsatile secretion of biologically active luteinizing hormone in man.

J D Veldhuis, M L Dufau
PMCID: PMC442284  PMID: 3305575

Abstract

We investigated the effects of estradiol on bioactive luteinizing hormone (LH) release in normal men using two complementary strategies: (i) steady state intravenous infusions of estradiol at its endogenous production rate, and (ii) oral administration of the antiestrogen, tamoxifen HCl. Immunoreactive and biologically active LH were monitored by radioimmunoassay and the rat interstitial cell testosterone bioassay, respectively. Estradiol infusions significantly suppressed mean plasma bioactive LH concentrations and decreased the bio/immuno LH ratio. Conversely, antiestrogen treatment enhanced spontaneous bioactive LH pulse frequency, increased bioactive LH pulse amplitude, and augmented plasma intrapulse and interpulse bio/immuno LH ratios. Low-dose pulsed injections of exogenous gonadotropin-releasing hormone (GnRH) also increased plasma bio/immuno LH ratios. However, tamoxifen attenuated the ability of exogenous GnRH to further enhance the bio/immuno LH ratio, which suggests that endogenous LH release was already maximally enriched in LH bioactivity during antiestrogen administration. We conclude that estradiol modulates the pulsatile secretion of LH molecules enriched in biological activity in man.

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Selected References

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  1. Beitins I. Z., Dufau M. L., O'Loughlin K., Catt K. J., McArthur J. W. Analysis of biological and immunological activities in the two pools of LH released during constant infusion of luteinizing hormone-releasing hormone (LHRH) in men. J Clin Endocrinol Metab. 1977 Sep;45(3):605–608. doi: 10.1210/jcem-45-3-605. [DOI] [PubMed] [Google Scholar]
  2. Boyar R. M., Perlow M., Kapen S., Lefkowitz G., Weitzman E., Hellman L. The effect of clomiphene citrate on the 24-hour LH secretory pattern in normal men. J Clin Endocrinol Metab. 1973 Mar;36(3):561–567. doi: 10.1210/jcem-36-3-561. [DOI] [PubMed] [Google Scholar]
  3. Clarke I. J., Cummins J. T. The temporal relationship between gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) secretion in ovariectomized ewes. Endocrinology. 1982 Nov;111(5):1737–1739. doi: 10.1210/endo-111-5-1737. [DOI] [PubMed] [Google Scholar]
  4. Davis M. R., Veldhuis J. D., Rogol A. D., Dufau M. L., Catt K. J. Sustained inhibitory actions of a potent antagonist of gonadotropin-releasing hormone in postmenopausal women. J Clin Endocrinol Metab. 1987 Jun;64(6):1268–1274. doi: 10.1210/jcem-64-6-1268. [DOI] [PubMed] [Google Scholar]
  5. Drouin J., Labrie F. Interactions between 17 beta-estradiol and progesterone in the control of luteinizing hormone and follicle-stimulating hormone release in rat anterior pituitary cells in culture. Endocrinology. 1981 Jan;108(1):52–57. doi: 10.1210/endo-108-1-52. [DOI] [PubMed] [Google Scholar]
  6. Dufau M. L., Beitins I. Z., McArthur J. W., Catt K. J. Effects of luteinizing hormone releasing hormone (LHRH) upon bioactive and immunoreactive serum LH levels in normal subjects. J Clin Endocrinol Metab. 1976 Sep;43(3):658–667. doi: 10.1210/jcem-43-3-658. [DOI] [PubMed] [Google Scholar]
  7. Dufau M. L., Pock R., Neubauer A., Catt K. J. In vitro bioassay of LH in human serum: the rat interstitial cell testosterone (RICT) assay. J Clin Endocrinol Metab. 1976 May;42(5):958–969. doi: 10.1210/jcem-42-5-958. [DOI] [PubMed] [Google Scholar]
  8. Dufau M. L., Veldhuis J. D., Fraioli F., Johnson M. L., Beitins I. Z. Mode of secretion of bioactive luteinizing hormone in man. J Clin Endocrinol Metab. 1983 Nov;57(5):993–1000. doi: 10.1210/jcem-57-5-993. [DOI] [PubMed] [Google Scholar]
  9. Kohler P. O., Ross G. T., Odell W. D. Metabolic clearance and production rates of human luteinizing hormone in pre- and postmenopausal women. J Clin Invest. 1968 Jan;47(1):38–47. doi: 10.1172/JCI105713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Levine J. E., Ramirez V. D. Luteinizing hormone-releasing hormone release during the rat estrous cycle and after ovariectomy, as estimated with push-pull cannulae. Endocrinology. 1982 Nov;111(5):1439–1448. doi: 10.1210/endo-111-5-1439. [DOI] [PubMed] [Google Scholar]
  11. Lobo R. A., Shoupe D., Chang S. P., Campeau J. The control of bioactive luteinizing hormone secretion in women with polycystic ovary syndrome. Am J Obstet Gynecol. 1984 Feb 15;148(4):423–428. doi: 10.1016/0002-9378(84)90720-8. [DOI] [PubMed] [Google Scholar]
  12. Lucky A. W., Rebar R. W., Rosenfield R. L., Roche-Bender N., Helke J. Reduction of the potency of luteinizing hormone by estrogen. N Engl J Med. 1979 May 3;300(18):1034–1036. doi: 10.1056/NEJM197905033001808. [DOI] [PubMed] [Google Scholar]
  13. Marut E. L., Williams R. F., Cowan B. D., Lynch A., Lerner S. P., Hodgen G. D. Pulsatile pituitary gonadotropin secretion during maturation of the dominant follicle in monkeys: estrogen positive feedback enhances the biological activity of LH. Endocrinology. 1981 Dec;109(6):2270–2272. doi: 10.1210/endo-109-6-2270. [DOI] [PubMed] [Google Scholar]
  14. Miyake A., Tasaka K., Sakumoto T., Kawamura Y., Nagahara Y., Aono T. Clomiphene citrate induces luteinizing hormone release through hypothalamic luteinizing hormone-releasing hormone in vitro. Acta Endocrinol (Copenh) 1983 Jul;103(3):289–292. doi: 10.1530/acta.0.1030289. [DOI] [PubMed] [Google Scholar]
  15. Pollack L., Atkinson P. H. Correlation of glycosylation forms with position in amino acid sequence. J Cell Biol. 1983 Aug;97(2):293–300. doi: 10.1083/jcb.97.2.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rajalakshmi M., Robertson D. M., Choi S. K., Diczfalusy E. Biologically active luteinizing hormone (LH) in plasma. III. Validation of the in vitro bioassay when applied to male plasma and the possible role of steroidal precursors. Acta Endocrinol (Copenh) 1979 Apr;90(4):585–598. [PubMed] [Google Scholar]
  17. Santen R. J., Bardin C. W. Episodic luteinizing hormone secretion in man. Pulse analysis, clinical interpretation, physiologic mechanisms. J Clin Invest. 1973 Oct;52(10):2617–2628. doi: 10.1172/JCI107454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Santen R. J., Ruby E. B. Enhanced frequency and magnitude of episodic luteinizing hormone-releasing hormone discharge as a hypothalamic mechanism for increased luteinizing hormone secretion. J Clin Endocrinol Metab. 1979 Feb;48(2):315–319. doi: 10.1210/jcem-48-2-315. [DOI] [PubMed] [Google Scholar]
  19. Solano A. R., Dufau M. L., Catt K. J. Bioassay and radioimmunoassay of serum luteinizing hormone in the male rat. Endocrinology. 1979 Aug;105(2):372–381. doi: 10.1210/endo-105-2-372. [DOI] [PubMed] [Google Scholar]
  20. Solano A. R., Garcia-Vela A., Catt K. J., Dufau M. L. Modulation of serum and pituitary luteinizing hormone bioactivity by androgen in the rat. Endocrinology. 1980 Jun;106(6):1941–1948. doi: 10.1210/endo-106-6-1941. [DOI] [PubMed] [Google Scholar]
  21. Sutherland R., Mester J., Baulieu E. E. Tamoxifen is a potent "pure" anti-oestrogen in chick oviduct. Nature. 1977 Jun 2;267(5610):434–435. doi: 10.1038/267434a0. [DOI] [PubMed] [Google Scholar]
  22. Veldhuis J. D., Beitins I. Z., Johnson M. L., Serabian M. A., Dufau M. L. Biologically active luteinizing hormone is secreted in episodic pulsations that vary in relation to stage of the menstrual cycle. J Clin Endocrinol Metab. 1984 Jun;58(6):1050–1058. doi: 10.1210/jcem-58-6-1050. [DOI] [PubMed] [Google Scholar]
  23. Veldhuis J. D., Johnson M. L. Cluster analysis: a simple, versatile, and robust algorithm for endocrine pulse detection. Am J Physiol. 1986 Apr;250(4 Pt 1):E486–E493. doi: 10.1152/ajpendo.1986.250.4.E486. [DOI] [PubMed] [Google Scholar]
  24. Veldhuis J. D., Rogol A. D., Johnson M. L. Endogenous opiates modulate the pulsatile secretion of biologically active luteinizing hormone in man. J Clin Invest. 1983 Dec;72(6):2031–2040. doi: 10.1172/JCI111168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Veldhuis J. D., Rogol A. D., Samojlik E., Ertel N. H. Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man. J Clin Invest. 1984 Jul;74(1):47–55. doi: 10.1172/JCI111417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Veldhuis J. D., Sowers J. R., Rogol A. D., Klein F. A., Miller N., Dufau M. L. Pathophysiology of male hypogonadism associated with endogenous hyperestrogenism. Evidence for dual defects in the gonadal axis. N Engl J Med. 1985 May 23;312(21):1371–1375. doi: 10.1056/NEJM198505233122107. [DOI] [PubMed] [Google Scholar]
  27. Wehmann R. E., Blackman M. R., Harman S. M. Metabolic clearance rates of luteinizing hormone in women during different phases of the menstrual cycle and while taking an oral contraceptive. J Clin Endocrinol Metab. 1982 Oct;55(4):654–659. doi: 10.1210/jcem-55-4-654. [DOI] [PubMed] [Google Scholar]
  28. Winters S. J., Troen P. Evidence for a role of endogenous estrogen in the hypothalamic control of gonadotropin secretion in men. J Clin Endocrinol Metab. 1985 Nov;61(5):842–845. doi: 10.1210/jcem-61-5-842. [DOI] [PubMed] [Google Scholar]

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