Skip to main content
Log in

Response of the Primate Secretory Endometrium to Subchronic Hypercortisolemia

  • Published:
The Journal of the Society for Gynecologic Investigation: JSGI Aims and scope Submit manuscript

Abstract

Objective

To assess the impact of subchronic and moderate hypercortisolism on the secretory endometrium of the cynomolgus monkey.

Methods

Osmotic pumps containing hydrocortisone phosphate (HP) were implanted subcutaneously in each monkey on the first day of the menstrual cycle; each monkey also received pumps containing saline in another cycle. Blood was obtained three times per week and urine was collected daily for hormone analyses. Endometriectomy was performed 13 ± 1 days after the serum estradiol (E2) peak in each study cycle.

Results

Infusion of HP elevated serum Cortisol levels by an average of 70%. Mean serum progesterone (P) levels were decreased by 50% during the secretory phase of HP-treatment cycles by comparison with self-control cycles (9 <.01); as a result, the mean endometrial glycogen concentration was reduced by 30% (P <.05) and the activity of 17$-hydroxysteroid dehydrogenase was decreased by 70% (P <.05). Serum E2 levels were not consistently elevated by HP treatment, but cytosolic estrogen receptor levels of the endometrium were decreased by 50%) (P <.01), indicating increased estrogenic stimulation. Histologic development of the secretory endometrium was retarded, but the length of the secretory phase was not affected by the treatment.

Conclusion

A moderate elevation of serum Cortisol levels over one menstrual cycle consistently produced a reduction in serum P and a hypoprogestogenic-hyperestrogenic response of the secretory endometrium in the cynomolgus monkey, (J Soc Gynecol Invest 1997;4:152-159)

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Campbell PS. The mechanism of the inhibition of uterotrophic responses by acute dexamethasone pretreatment. Endocrinology 1978;103:716–23.

    Article  CAS  Google Scholar 

  2. Rabin DS, Johnson EO, Brandon DD, Liapi C, Chrousos GP. Glucocorticoids inhibit estradiol-mediated uterine growth: Possible role of the uterine estradiol receptor. Biol Reprod 1990;42: 74–80.

    Article  CAS  Google Scholar 

  3. Hayashi KT, Moberg GP. Influence of the hypothalamic-pituitary-adrenal axis on the menstrual cycle and the pituitary responsiveness to estradiol in the female rhesus monkey (Macaca mulatta). Biol Reprod 1990;42:260–5.

    Article  CAS  Google Scholar 

  4. Kowalski W, Chatterton RT Jr. Effects of subchronic implantation of hydrocortisone phosphate-releasing osmotic pumps on peripheral gonadotropin levels and estradiol feedback to gonadotropin secretion in the cynomolgus monkey. Neuroendocrinology 1993;57:330–9.

    Article  CAS  Google Scholar 

  5. Chatterton RT Jr, Kazer RR, Rebar RW. Depletion of luteal phase serum progesterone during constant infusion of Cortisol phosphate in the cvnomolgus monkey. Fertil Steril 1991;56:547–54.

    Article  Google Scholar 

  6. Hagino N. The effect of synthetic corticosteroids on ovarian function in the baboon. J Clin Endocrinol Metab 1972;35:716–21.

    Article  CAS  Google Scholar 

  7. Stanczyk FZ, Petra PH, SennerJW, Now MJ. Effect of dexa-methasone treatment on sex steroid-binding protein, corticoste-roid-binding globulin, and steroid hormones in cycling rhesus macaques. Am J Obstet Gynecol 1985;151:464–70.

    Article  CAS  Google Scholar 

  8. Keller-Wood ME, Dallman MF. Corticosteroid inhibition of ACTH secretion. Endocr Rev 1984;5:1–24.

    Article  CAS  Google Scholar 

  9. Siiteri PK. Obesity and peripheral estrogen synthesis. In: Frisch RE, ed. Adipose tissue and reproduction. Basel: Karger, 1990: 70–84.

    Google Scholar 

  10. Villanueva AL, Schlosser C, Hopper B, Liu JH, Hoffrnan DI, Rebar RW. Increased Cortisol production in women runners. J Clin Endocrinol Metab 1986;63:133–6.

    Article  CAS  Google Scholar 

  11. Suh BY, Liu JH, Berga SL, Laughlin GA, Yen SSC. Hypercor-tisolism in patients with functional hypothalamic amenorrhea. J Clin Endocnnol Metab 1988;66:733–9.

    Article  CAS  Google Scholar 

  12. Wentz AC. Endometrial biopsy in the evaluation of infertility. Fertil Steril 1980;33:121–4.

    Article  CAS  Google Scholar 

  13. Kowalski W, Chatterton RT Jr. Peripheral and not central suppression of ovarian function during osmotic pump infusion of adrenocorticotropin-(1-24) for one menstrual cycle in the cynomolgus monkey and its partial compensation by a transitory elevation of sex hormone-binding globulin levels. Endocrinology 1992;130:3582–92.

    Article  CAS  Google Scholar 

  14. Padykula HA. Regeneration of the primate uterus: The role of stem cells. Ann NY Acad Sci 1991;622:47–56.

    Article  CAS  Google Scholar 

  15. Kowalski W, Chatterton RT Jr, Kazer RR, Wentz AC. The impact of subchronic hypercortisolemia on progesterone metabolism and the luteinizing hormone-progesterone axis in the cynomolgus monkey. J Clin Endocrinol Metab 1993;77:1597–604.

    CAS  PubMed  Google Scholar 

  16. Tseng L, Gurpide E. Estradiol and 20a-dihydroprogesterone dehydrogenase activities in human endometrium during the menstrual cycle. Endocrinology 1974;94:419–23.

    Article  CAS  Google Scholar 

  17. Tseng L. Hormonal regulation of steroid metabolic enzymes in human endometrium. In: Thomas JA, Singhal RL, eds. Advances in sex hormone research. Vol. 4. Baltimore: Urban and Schwarzenberg, 1980:329–361.

    Google Scholar 

  18. Gonnley GJ, Hospelhorn VD, Khan MK, Jensen EV. A controlled pore glass bead assay for the measurement of cytoplasmic and nuclear glucocorticoid receptors. J Steroid Biochem 1985 22:693–698.

    Article  Google Scholar 

  19. Greene GL, Nolan C, Engler JP, Jensen EV. Monoclonal antibodies to human estrogen receptor. Proc Nad Acad Sci USA 1980;77:5115–9.

    Article  CAS  Google Scholar 

  20. Greene GL, Sobel NB, King WJ, Jensen EV. Immunochemical studies of estrogen receptors. J Steroid Biochem 1984;20:51–6.

    Article  CAS  Google Scholar 

  21. West NB, McClellan MC, Sternfeld MD, Brenner RM. Immunocytochemistry versus binding assays of the estrogen receptor in the reproductive tract of spayed and hormone-treated macaques. Endocrinology 1987;121:1789–800.

    Article  CAS  Google Scholar 

  22. Brenner RM, West NB, McClellan MC. Estrogen and progestin receptors in the reproductive tract of male and female primates. Biol Reprod 1990;42:11–9.

    Article  CAS  Google Scholar 

  23. Huijing F. A rapid enzymic method for glycogen estimation in very small tissue samples. Clin Chim Acta 1970;30:567–72.

    Article  CAS  Google Scholar 

  24. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–54.

    Article  CAS  Google Scholar 

  25. Hinegardner RT. An improved fluorometric assay for DNA. Anal Biochem 1971;39:197–201.

    Article  CAS  Google Scholar 

  26. Bardawil WA. Endometrium. In: Gold JJ, Josimovich JB, eds. Gynecologic endocrinology. New York: Plenum, 1987:185–244.

    Chapter  Google Scholar 

  27. Brenner PJvl, Carlisle KS, Hess DL, Sandow BA, West NB. Morphology of the oviducts and endometria of cynomolgus macaques during the menstrual cycle. Biol Reprod 1983;29: 1289–302.

    Article  CAS  Google Scholar 

  28. Tseng L, Gurpide E. Induction of human endometrial estradiol dehydrogenase by progestins. Endocrinology 1975;97:825–33.

    Article  CAS  Google Scholar 

  29. Mildwisky A, Paid Z, Gutman A. Glycogen metabolism of the human endometrium. J Clin Endocrinol Metab 1980;51:765–70.

    Article  Google Scholar 

  30. Macdonald GJ, Demers LM, Greep RO. Peripheral serum progesterone and correlated endometrial glycogen levels during the menstrual cycle of Macaca arctoides. Fertil Steril 1973;24:98–103.

    Article  CAS  Google Scholar 

  31. Mimori H, Fukuma K, Matsuo I, Nakahara K, Maeyama M. Effect of progestogen on glycogen metabolism in the endometrium of infertile patients during the menstrual cycle. Fertil Steril 1981;35:289–95.

    Article  CAS  Google Scholar 

  32. Tseng L, Stolee A, Gurpide E. Quantitative studies on the uptake and metabolism of estrogens and progesterone by human endometrium. Endocrinology 1972;90:390–404.

    Article  CAS  Google Scholar 

  33. Huang Jr, Bellino FL, Osawa Y, Tseng L. Immunologic identification of the aromatase enzyme system in human endometrium. J Steroid Biochem 1989;33:1043–7.

    Article  CAS  Google Scholar 

  34. Simpson ER, Merrill JC, Hollub AJ, Graham-Lorence S, Mendelson CR. Regulation of estrogen biosynthesis by human adipose cells. Endocr Rev 1989;10:136–48.

    Article  CAS  Google Scholar 

  35. Ankenbauer W, Strahle U, Schutz G. Synergistic action of glucocorticoid and estradiol responsive elements. Proc Natl Acad Sci USA 1988;85:7526–30.

    Article  CAS  Google Scholar 

  36. Borras M, Hardy L, Lempereur F, et al. Estradiol-induced down-regulation of estrogen receptor. Effect of various modulators of protein synthesis and expression. J Steroid Biochem Mol Biol 1994;48:325–36.

    Article  CAS  Google Scholar 

  37. Kreitmann-Gimbal B, Goodman AL, Bayard F, Hodgen GD. Characterization of estrogen and progesterone receptors in monkey endometrium: Methodology and effects of estradiol and/or progesterone on endometrium of castrate monkeys. Steroids 1979;34:749–69.

    Article  CAS  Google Scholar 

  38. Schmidt-Gollwitzer M, Genz T, Schmidt-Gollwitzer K, Pollow B, Pollow K. Correlation between oestradiol and progesterone receptor levels, 17α-hydroxysteroid dehydrogenase activity and endometrial tissue levels of oestradiol, oestrone and progesterone in women. In: Brush MG, King RJB, Taylor RW, eds. Endometrial cancer. London: Tindall, 1977:227–241.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This study was supported by a grant from the National Institutes of Health, P01 HD 21921. and a Biomedical Research Support Grant from Northwestern University Medical School, Chicago. Illinois. The authors thank Drs. Anne Colsron Wentz and Wadi A. Bardawil for assessment of endometrial morphology.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kowalski, W.B., Valle, R.F. & Chatterton, R.T. Response of the Primate Secretory Endometrium to Subchronic Hypercortisolemia. Reprod. Sci. 4, 152–159 (1997). https://doi.org/10.1177/107155769700400307

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/107155769700400307

Key words

Navigation