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. 1986 Oct;78(4):870–873. doi: 10.1172/JCI112673

Testosterone and estradiol are co-secreted episodically by the human testis.

S J Winters, P Troen
PMCID: PMC423704  PMID: 3760188

Abstract

In spite of a striking pulsatile pattern of luteinizing hormone (LH) secretion, testosterone (T) fluctuations in peripheral blood in normal adult men are irregular and of low amplitude. To determine whether T secretion by the human testis is episodic, T was measured in blood samples drawn at 15-min intervals for 4 h through a catheter placed in the testicular vein of six men with varicocele-associated infertility. Estradiol (E2) concentrations were also determined in each sample. Each subject released testosterone in well-defined pulses. Gonadal vein T levels ranged from 1 to 1,540 ng/ml. Mean (+/- SE) pulse amplitude was 176 +/- 42 ng/ml, with a frequency of 4.0 +/- 0.3 pulses per 4 h. Testicular vein E2 levels ranged from 0.01 to 6.8 ng/ml. E2 secretory episodes were generally coincident with T pulses, and their amplitudes were highly positively correlated (r = 0.90, P less than 0.01). These results indicate that T secretion by the adult human testis is pulsatile, and suggest a functional relationship between intermittent LH secretion and normal testicular steroidogenesis in men. The failure to appreciate these fluctuations as hormone pulses in peripheral blood may relate to their absolute amplitude and frequency. The concordance between E2 and T pulses suggests that the Leydig cell, under LH control, is the source of most of the E2 secreted by the adult human testis.

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Selected References

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  1. Belchetz P. E., Plant T. M., Nakai Y., Keogh E. J., Knobil E. Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone. Science. 1978 Nov 10;202(4368):631–633. doi: 10.1126/science.100883. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Coquelin A., Desjardins C. Luteinizing hormone and testosterone secretion in young and old male mice. Am J Physiol. 1982 Sep;243(3):E257–E263. doi: 10.1152/ajpendo.1982.243.3.E257. [DOI] [PubMed] [Google Scholar]
  4. D'Occhio M. J., Schanbacher B. D., Kinder J. E. Relationship between serum testosterone concentration and patterns of luteinizing hormone secretion in male sheep. Endocrinology. 1982 May;110(5):1547–1554. doi: 10.1210/endo-110-5-1547. [DOI] [PubMed] [Google Scholar]
  5. Davies T. F., Hodgen G. D., Dufau M. L., Catt K. J. Regulation of primate testicular luteinizing hormone receptors and steroidogenesis. J Clin Invest. 1979 Oct;64(4):1070–1073. doi: 10.1172/JCI109545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DePalatis L., Moore J., Falvo R. E. Plasma concentrations of testosterone and LH in the male dog. J Reprod Fertil. 1978 Mar;52(2):201–207. doi: 10.1530/jrf.0.0520201. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Green K. F., Turner T. T., Howards S. S. Varicocele: reversal of the testicular blood flow and temperature effects by varicocele repair. J Urol. 1984 Jun;131(6):1208–1211. doi: 10.1016/s0022-5347(17)50874-5. [DOI] [PubMed] [Google Scholar]
  9. Hammond G. L., Ruokonen A., Kontturi M., Koskela E., Vihko R. The simultaneous radioimmunoassay of seven steroids in human spermatic and peripheral venous blood. J Clin Endocrinol Metab. 1977 Jul;45(1):16–24. doi: 10.1210/jcem-45-1-16. [DOI] [PubMed] [Google Scholar]
  10. Hodgson Y. M., Urquhart G., de Kretser D. M. Effect of oestradiol and tamoxifen on the testosterone response in male rats to a single injection of hCG. J Reprod Fertil. 1983 Jul;68(2):295–304. doi: 10.1530/jrf.0.0680295. [DOI] [PubMed] [Google Scholar]
  11. Huhtaniemi I., Bolton N., Leinonen P., Kontturi M., Vihko R. Testicular luteinizing hormone receptor content and in vitro stimulation of cyclic adenosine 3',5'-monophosphate and steroid production: a comparison between man and rat. J Clin Endocrinol Metab. 1982 Nov;55(5):882–889. doi: 10.1210/jcem-55-5-882. [DOI] [PubMed] [Google Scholar]
  12. Ito T., Horton R. The source of plasma dihydrotestosterone in man. J Clin Invest. 1971 Aug;50(8):1621–1627. doi: 10.1172/JCI106650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jones G. E., Baker K., Fahmy D. R., Boyns A. R. Effect of luteinizing hormone releasing hormone on plasma levels of luteinizing hormone, oestradiol and testosterone in the male dog. J Endocrinol. 1976 Mar;68(3):469–474. doi: 10.1677/joe.0.0680469. [DOI] [PubMed] [Google Scholar]
  14. Judd H. L., Rebar R., Vandenberg G., Yen S. S. Effect of luteinizing hormone-releasing factor on Leydig cell function. J Clin Endocrinol Metab. 1974 Jan;38(1):8–13. doi: 10.1210/jcem-38-1-8. [DOI] [PubMed] [Google Scholar]
  15. Katongole C. B., Naftolin F., Short R. V. Relationship between blood levels of luteinizing hormone and testosterone in bulls, and the effects of sexual stimulation. J Endocrinol. 1971 Jul;50(3):457–466. doi: 10.1677/joe.0.0500457. [DOI] [PubMed] [Google Scholar]
  16. Lacroix A., Pelletier J. LH and testosterone release in developing bulls following LH-RH treatment. Effect of gonadectomy and chronic testosterone propionate pre-treatment. Acta Endocrinol (Copenh) 1979 Aug;91(4):719–729. doi: 10.1530/acta.0.0910719. [DOI] [PubMed] [Google Scholar]
  17. Leinonen P. Estrone and estradiol concentrations in the testis and spermatic and peripheral venous blood of elderly men: the influence of estrogen treatment. J Steroid Biochem. 1980 Jul;13(7):737–742. doi: 10.1016/0022-4731(80)90225-3. [DOI] [PubMed] [Google Scholar]
  18. Leymarie P., Roger M., Castanier M., Scholler R. Circadian variations of plasma testosterone and estrogens in normal men. A study by frequent sampling. J Steroid Biochem. 1974 Apr;5(2):167–171. doi: 10.1016/0022-4731(74)90124-1. [DOI] [PubMed] [Google Scholar]
  19. Lincoln G. A., Kay R. N. Effects of season on the secretion of LH and testosterone in intact and castrated red deer stags (Cervus elaphus). J Reprod Fertil. 1979 Jan;55(1):75–80. doi: 10.1530/jrf.0.0550075. [DOI] [PubMed] [Google Scholar]
  20. Lincoln G. A. Seasonal variation in the episodic secretion of luteinizing hormone and testosterone in the ram. J Endocrinol. 1976 May;69(2):213–226. doi: 10.1677/joe.0.0690213. [DOI] [PubMed] [Google Scholar]
  21. Moor B. C., Younglai E. V. Variations in peripheral levels of LH and testosterone in adult male rabbits. J Reprod Fertil. 1975 Feb;42(2):259–266. doi: 10.1530/jrf.0.0420259. [DOI] [PubMed] [Google Scholar]
  22. Murray M. A., Corker C. S. Levels of testosterone and luteinizing hormone in plasma samples taken at 10-minute intervals in normal men. J Endocrinol. 1973 Jan;56(1):157–158. doi: 10.1677/joe.0.0560157. [DOI] [PubMed] [Google Scholar]
  23. Naftolin F., Judd H. L., Yen S. S. Pulsatile patterns of gonadotropins and testosterone in man: the effects of clomiphene, with and without testosterone added. J Clin Endocrinol Metab. 1973 Feb;36(2):285–288. doi: 10.1210/jcem-36-2-285. [DOI] [PubMed] [Google Scholar]
  24. Nankin H. R., Troen P. Repetitive luteinizing hormone elevations in serum of normal men. J Clin Endocrinol Metab. 1971 Sep;33(3):558–560. doi: 10.1210/jcem-33-3-558. [DOI] [PubMed] [Google Scholar]
  25. Nisula B. C., Loriaux D. L., Wilson Y. A. Solid phase method for measurement of the binding capacity of testosterone-estradiol binding globulin in human serum. Steroids. 1978 May;31(5):681–690. doi: 10.1016/s0039-128x(78)80008-7. [DOI] [PubMed] [Google Scholar]
  26. Payne A. H., Kelch R. P., Musich S. S., Halpern M. E. Intratesticular site of aromatization in the human. J Clin Endocrinol Metab. 1976 Jun;42(6):1081–1087. doi: 10.1210/jcem-42-6-1081. [DOI] [PubMed] [Google Scholar]
  27. Plant T. M. Time courses of concentrations of circulating gonadotropin, prolactin, testosterone, and cortisol in adult male rhesus monkeys (Macaca mulatta) throughout the 24 h light-dark cycle. Biol Reprod. 1981 Sep;25(2):244–252. doi: 10.1095/biolreprod25.2.244. [DOI] [PubMed] [Google Scholar]
  28. Rowe P. H., Racey P. A., Lincoln G. A., Ellwood M., Lehane J., Shenton J. C. The temporal relationship between the secretion of luteinizing hormone and testosterone in man. J Endocrinol. 1975 Jan;64(1):17–26. [PubMed] [Google Scholar]
  29. Saez J. M., Forest M. G. Kinetics of human chorionic gonadotropin-induced steroidogenic response of the human testis. I. Plasma testosterone: implications for human chorionic gonadotropin stimulation test. J Clin Endocrinol Metab. 1979 Aug;49(2):278–283. doi: 10.1210/jcem-49-2-278. [DOI] [PubMed] [Google Scholar]
  30. Sanford L. M., Winter J. S., Palmer W. M., Howland B. E. The profile of LH and testosterone secretion in the ram. Endocrinology. 1974 Aug;95(2):627–631. doi: 10.1210/endo-95-2-627. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Sholl S. A., Toivola P. T., Robinson J. A. The dynamics of testosterone and dihydrotestosterone metabolism in the adult male rhesus monkey. Endocrinology. 1979 Aug;105(2):402–405. doi: 10.1210/endo-105-2-402. [DOI] [PubMed] [Google Scholar]
  33. Smith K. D., Tcholakian R. K., Chowdhury M., Steinberger E. Rapid oscillations in plasma levels of testosterone, luteinizing hormone, and follicle-stimulating hormone in men. Fertil Steril. 1974 Nov;25(11):965–975. [PubMed] [Google Scholar]
  34. Steiner R. A., Peterson A. P., Yu J. Y., Conner H., Gilbert M., terPenning B., Bremner W. J. Ultradian luteinizing hormone and testosterone rhythms in the adult male monkey, Macaca fascicularis. Endocrinology. 1980 Nov;107(5):1489–1493. doi: 10.1210/endo-107-5-1489. [DOI] [PubMed] [Google Scholar]
  35. Takahashi J., Higashi Y., LaNasa J. A., Winters S. J., Oshima H., Troen P. Studies of the human testis. XVII. Gonadotropin regulation of intratesticular testosterone and estradiol in infertile men. J Clin Endocrinol Metab. 1982 Dec;55(6):1073–1080. doi: 10.1210/jcem-55-6-1073. [DOI] [PubMed] [Google Scholar]
  36. Takahashi J., Higashi Y., LaNasa J. A., Yoshida K., Winters S. J., Oshima H., Troen P. Studies of the human testis. XVIII. Simultaneous measurement of nine intratesticular steroids: evidence for reduced mitochondrial function in testis of elderly men. J Clin Endocrinol Metab. 1983 Jun;56(6):1178–1187. doi: 10.1210/jcem-56-6-1178. [DOI] [PubMed] [Google Scholar]
  37. Toivola P. T., Bridson W. E., Robinson J. A. Effect of luteinizing hormone-releasing hormone on the secretion of luteinizing hormone, follicle-stimulating hormone, and testosterone in adult male rhesus monkeys. Endocrinology. 1978 Jun;102(6):1815–1815. doi: 10.1210/endo-102-6-1815. [DOI] [PubMed] [Google Scholar]
  38. Tsai-Morris C. H., Aquilano D. R., Dufau M. L. Cellular localization of rat testicular aromatase activity during development. Endocrinology. 1985 Jan;116(1):38–46. doi: 10.1210/endo-116-1-38. [DOI] [PubMed] [Google Scholar]
  39. Veldhuis J. D., Evans W. S., Rogol A. D., Drake C. R., Thorner M. O., Merriam G. R., Johnson M. L. Intensified rates of venous sampling unmask the presence of spontaneous, high-frequency pulsations of luteinizing hormone in man. J Clin Endocrinol Metab. 1984 Jul;59(1):96–102. doi: 10.1210/jcem-59-1-96. [DOI] [PubMed] [Google Scholar]
  40. Weinstein R. L., Kelch R. P., Jenner M. R., Kaplan S. L., Grumbach M. M. Secretion of unconjugated androgens and estrogens by the normal and abnormal human testis before and after human chorionic gonadotropin. J Clin Invest. 1974 Jan;53(1):1–6. doi: 10.1172/JCI107526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Winters S. J., Troen P. Pulsatile secretion of immunoreactive alpha-subunit in man. J Clin Endocrinol Metab. 1985 Feb;60(2):344–348. doi: 10.1210/jcem-60-2-344. [DOI] [PubMed] [Google Scholar]
  42. Yoshida K., LaNasa J. A., Jr, Takahashi J., Winters S. J., Oshima H., Troen P. Studies of the human testis. XVI. Evaluation of multiple indexes of testicular function in relation to advanced age, idiopathic oligospermia, or varicocele. Fertil Steril. 1982 Dec;38(6):712–720. doi: 10.1016/s0015-0282(16)46699-9. [DOI] [PubMed] [Google Scholar]

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