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. 1987 Dec;84(23):8745–8749. doi: 10.1073/pnas.84.23.8745

Unexpected responses of the hypothalamic gonadotropin-releasing hormone "pulse generator" to physiological estradiol inputs in the absence of the ovary.

J S Kesner 1, R C Wilson 1, J M Kaufman 1, J Hotchkiss 1, Y Chen 1, H Yamamoto 1, R R Pardo 1, E Knobil 1
PMCID: PMC299623  PMID: 3317420

Abstract

In the rhesus monkey (Macaca mulatta), the frequency of pulsatile gonadotropic hormone release is relatively constant in the face of widely varying levels of estradiol (E2) in the peripheral circulation--e.g., in the course of the follicular phase of the menstrual cycle and after ovariectomy. This suggests that modulation of the hypothalamic gonadotropin-releasing hormone (GnRH) "pulse generator" by this steroid is not of major physiological importance. Herein is described the unexpected inhibition or total blockade of the electrical activity of this pulse generator in ovariectomized monkeys by physiological levels of exogenous E2. This inhibition began 2-4.5 hr after the initiation of E2 infusion and was noted 1 to 3 weeks after subcutaneous implantation of E2-containing capsules. Pulse generator activity was also arrested during the initiation and subsequent development of estrogen-induced surges of luteinizing hormone. We propose that this inhibition of hypothalamic GnRH pulse generator activity by E2 in ovariectomized monkeys reflects the absence of an ovarian factor that normally protects this neuronal system from the inhibitory action of estrogen during the menstrual cycle.

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Selected References

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

  1. Baird D. T. Pulsatile secretion of LH and ovarian estradiol during the follicular phase of the sheep estrous cycle. Biol Reprod. 1978 Apr;18(3):359–364. doi: 10.1095/biolreprod18.3.359. [DOI] [PubMed] [Google Scholar]
  2. Bäckström C. T., McNeilly A. S., Leask R. M., Baird D. T. Pulsatile secretion of LH, FSH, prolactin, oestradiol and progesterone during the human menstrual cycle. Clin Endocrinol (Oxf) 1982 Jul 1;17(1):29–42. doi: 10.1111/j.1365-2265.1982.tb02631.x. [DOI] [PubMed] [Google Scholar]
  3. Dierschke D. J., Bhattacharya A. N., Atkinson L. E., Knobil E. Circhoral oscillations of plasma LH levels in the ovariectomized rhesus monkey. Endocrinology. 1970 Nov;87(5):850–853. doi: 10.1210/endo-87-5-850. [DOI] [PubMed] [Google Scholar]
  4. Filicori M., Santoro N., Merriam G. R., Crowley W. F., Jr Characterization of the physiological pattern of episodic gonadotropin secretion throughout the human menstrual cycle. J Clin Endocrinol Metab. 1986 Jun;62(6):1136–1144. doi: 10.1210/jcem-62-6-1136. [DOI] [PubMed] [Google Scholar]
  5. Gallo R. V. Pulsatile LH release during the ovulatory LH surge on proestrus in the rat. Biol Reprod. 1981 Feb;24(1):100–104. doi: 10.1095/biolreprod24.1.100. [DOI] [PubMed] [Google Scholar]
  6. Hotchkiss J., Atkinson L. E., Knobil E. Time course of serum estrogen and luteinizing hormone (LH) concentrations during the menstrual cycle of the rhesus monkey. Endocrinology. 1971 Jul;89(1):177–183. doi: 10.1210/endo-89-1-177. [DOI] [PubMed] [Google Scholar]
  7. Hotchkiss J., Dierschke D. J., Butler W. R., Fritz G. R., Knobil E. Relation between levels of circulating ovarian steroids and pituitary gonadotropin content during the menstrual cycle of the rhesus monkey. Biol Reprod. 1982 Mar;26(2):241–248. doi: 10.1095/biolreprod26.2.241. [DOI] [PubMed] [Google Scholar]
  8. Karsch F. J., Foster D. L., Bittman E. L., Goodman R. L. A role for estradiol in enhancing luteinizing hormone pulse frequency during the follicular phase of the estrous cycle of sheep. Endocrinology. 1983 Oct;113(4):1333–1339. doi: 10.1210/endo-113-4-1333. [DOI] [PubMed] [Google Scholar]
  9. Karsch F. J., Weick R. F., Butler W. R., Dierschke D. J., Krey L. C., Weiss G., Hotchkiss J., Yamaji T., Knobil E. Induced LH surges in the rhesus monkey: strength-duration characteristics of the estrogen stimulus. Endocrinology. 1973 Jun;92(6):1740–1747. doi: 10.1210/endo-92-6-1740. [DOI] [PubMed] [Google Scholar]
  10. Karsch F. J., Weick R. F., Hotchkiss J., Dierschke D. J., Knobil E. An analysis of the negative feedback control of gonadotropin secretion utilizing chronic implantation of ovarian steroids in ovariectomized rhesus monkeys. Endocrinology. 1973 Aug;93(2):478–486. doi: 10.1210/endo-93-2-478. [DOI] [PubMed] [Google Scholar]
  11. Knobil E. On the control of gonadotropin secretion in the rhesus monkey. Recent Prog Horm Res. 1974;30(0):1–46. doi: 10.1016/b978-0-12-571130-2.50005-5. [DOI] [PubMed] [Google Scholar]
  12. Knobil E., Plant T. M., Wildt L., Belchetz P. E., Marshall G. Control of the rhesus monkey menstrual cycle: permissive role of hypothalamic gonadotropin-releasing hormone. Science. 1980 Mar 21;207(4437):1371–1373. doi: 10.1126/science.6766566. [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. Nakai Y., Plant T. M., Hess D. L., Keogh E. J., Knobil E. On the sites of the negative and positive feedback actions of estradiol in the control of gonadotropin secretion in the rhesus monkey. Endocrinology. 1978 Apr;102(4):1008–1014. doi: 10.1210/endo-102-4-1008. [DOI] [PubMed] [Google Scholar]
  15. Norman R. L., Lindstrom S. A., Bangsberg D., Ellinwood W. E., Gliessman P., Spies H. G. Pulsatile secretion of luteinizing hormone during the menstrual cycle of rhesus macaques. Endocrinology. 1984 Jul;115(1):261–266. doi: 10.1210/endo-115-1-261. [DOI] [PubMed] [Google Scholar]
  16. Norman R. L., Spies H. G. Cyclic ovarian function in a male macaque: additional evidence for a lack of sexual differentiation in the physiological mechanisms that regulate the cyclic release of gonadotropins in primates. Endocrinology. 1986 Jun;118(6):2608–2610. doi: 10.1210/endo-118-6-2608. [DOI] [PubMed] [Google Scholar]
  17. Rahe C. H., Owens R. E., Fleeger J. L., Newton H. J., Harms P. G. Pattern of plasma luteinizing hormone in the cyclic cow: dependence upon the period of the cycle. Endocrinology. 1980 Aug;107(2):498–503. doi: 10.1210/endo-107-2-498. [DOI] [PubMed] [Google Scholar]
  18. Reame N., Sauder S. E., Kelch R. P., Marshall J. C. Pulsatile gonadotropin secretion during the human menstrual cycle: evidence for altered frequency of gonadotropin-releasing hormone secretion. J Clin Endocrinol Metab. 1984 Aug;59(2):328–337. doi: 10.1210/jcem-59-2-328. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Soules M. R., Steiner R. A., Clifton D. K., Cohen N. L., Aksel S., Bremner W. J. Progesterone modulation of pulsatile luteinizing hormone secretion in normal women. J Clin Endocrinol Metab. 1984 Feb;58(2):378–383. doi: 10.1210/jcem-58-2-378. [DOI] [PubMed] [Google Scholar]
  21. Van Vugt D. A., Lam N. Y., Ferin M. Reduced frequency of pulsatile luteinizing hormone secretion in the luteal phase of the rhesus monkey. Involvement of endogenous opiates. Endocrinology. 1984 Sep;115(3):1095–1101. doi: 10.1210/endo-115-3-1095. [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. Wilson R. C., Kesner J. S., Kaufman J. M., Uemura T., Akema T., Knobil E. Central electrophysiologic correlates of pulsatile luteinizing hormone secretion in the rhesus monkey. Neuroendocrinology. 1984 Sep;39(3):256–260. doi: 10.1159/000123988. [DOI] [PubMed] [Google Scholar]
  24. Yamaji T., Dierschke D. J., Bhattacharya A. N., Knobil E. The negative feedback control by estradiol and progesterone of LH secretion in the ovariectomized rhesus monkey. Endocrinology. 1972 Mar;90(3):771–777. doi: 10.1210/endo-90-3-771. [DOI] [PubMed] [Google Scholar]
  25. Yen S. S., Tsai C. C., Naftolin F., Vandenberg G., Ajabor L. Pulsatile patterns of gonadotropin release in subjects with and without ovarian function. J Clin Endocrinol Metab. 1972 Apr;34(4):671–675. doi: 10.1210/jcem-34-4-671. [DOI] [PubMed] [Google Scholar]

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