Skip to main content
SpringerLink
Log in

Serum levels of sex hormones and corticosterone throughout 4- and 5-day estrous cycles in Fischer 344 rats and their simulation in ovariectomized females

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Among inbred strains of rats, The Fischer 344 (F344) is commonly used in im-munological and behavioral studies. However, Little is known about patterns of sex hormones and corticosterone (CORT) secretion throughout the estrous cycle in this strain, Which is characterized by a marked CORT response to stress and variable length of cycles. In the current study, using radioimmunoassays, we assessed serum levels of progesterone, estradiol, LH, testosterone, prolactin and CORT, at 1-h intervals throughout the estrous cycle in F344 female rats with 4- and 5-day cycles, as well as in males. Vaginal smears were obtained from 268 females for 15 consecutive days to determine individual length of the estrous cycle and the exact estrous phase upon blood withdrawal, which was conducted once in each rat on the 12th day of smearing. The results indicated that both 4- and 5-day cyclers have two distinct and marked surges of progesterone, one on proestrus day and the other on diestrous-1 day. Testosterone levels in 5-day cyclers peaked on diestrus-3, one day earlier than in 4-day cyclers. Daily peak levels of CORT gradually increased from estrus day to proestrous day, whereas daily nadir levels of CORT remained unchanged. To simulate the natural kinetics of specific sex hormones in ovaries-tomized females, different doses of estradiol, progesterone, testosterone, prolactin or CORT were injected sc or ip, or 90-day sustained release pellets containing different doses of estradiol or progesterone were implanted. The findings indicated dose- and time-dependent effects, suggesting regimens for modeling the estrous cycle or replacement therapy.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Baldwin DM, Colombo JA, Sawyer CH. Plasma prolactin, LH, And corticosterone in rats exposed to A novel environment. Am J Physiol 1974, 226: 1366–9.

    PubMed  CAS  Google Scholar 

  2. LaPolt PS, Matt DW, Lu JK. Progesterone implants delay age-related declines in regular estrous cyclicity and the ovarian follicular reserve in Long-Evans rats. Biol Reprod 1998, 59: 197–201.

    Article  PubMed  CAS  Google Scholar 

  3. Smith ER, Bowers CY, Davidson JM. Circulating levels of plasma gonadotropins in 4- and 5-day cycling rats. Endocrinology 1973, 93: 756–8.

    Article  PubMed  CAS  Google Scholar 

  4. Arai K, Watanabe G, Taya K, Sasamoto S. Roles of inhibin and estradiol in the regulation of follicle-stimulating hormone and luteinizing hormone secretion during the estrous cycle of the rat. Biol Reprod 1996, 55: 127–33.

    Article  PubMed  CAS  Google Scholar 

  5. Lapolt PS, Yu SM, Lu JK. Early treatment of young female rats with progesterone delays the aging-associated reproductive decline: a counteraction by estradiol. Biol Reprod 1988, 38: 987–95.

    Article  PubMed  CAS  Google Scholar 

  6. Smith MS, Fox SR, Chatterton RT. Role of proestrous progesterone secretion in suppressing basal pulsatile LH secretion during estrus of the estrous cycle. Neuroendocrinology 1989, 50: 308–14.

    Article  PubMed  CAS  Google Scholar 

  7. Ando-Lu J, Sasahara K, Nishiyama K, Et Al. Strain-differences in proliferative activity of uterine endometrial cells in donryu and Fischer 344 rats. Exp Toxicol Pathol 1998, 50: 185–90.

    Article  PubMed  CAS  Google Scholar 

  8. Eldridge JC, Fleenor-Heyser DG, Extrom PC, Et Al. Short-term effects of chlorotriazines on estrus in female Sprague-Dawley and Fischer 344 rats. J Toxicol Environ Health 1994, 43: 155–67.

    Article  PubMed  CAS  Google Scholar 

  9. Naftolin F, Brown-Grant K, Corker CS. Plasma and pituitary luteinizing hormone and peripheral plasma oestradiol concentrations in the normal oestrous cycle of the rat and after experimental manipulation of the cycle. J Endocrinol 1972, 53: 17–30.

    Article  PubMed  CAS  Google Scholar 

  10. Smith CC, Omeljaniuk RJ, Whitfield HJ Jr., Et Al. Differential mineralocorticoid (Type 1) and glucocorticoid (Type 2) receptor expression in Lewis and Fischer rats. Neuroimmunomodulation 1994, 1: 66–73.

    Article  PubMed  CAS  Google Scholar 

  11. Wetzel LT, Luempert LG 3rd, Breckenridge CB, Et Al. Chronic effects of Atrazine on estrus and mammary tumor formation in female Sprague-Dawley and Fischer 344 rats. J Toxicol Environ Health 1994, 43: 169–82.

    Article  PubMed  CAS  Google Scholar 

  12. Kaneko S, Sato N, Sato K, Hashimoto I. Changes in plasma progesterone, estradiol, follicle-stimulating hormone and luteinizing hormone during diestrus and ovulation in rats with 5-day estrous cycles: effect of antibody against progesterone. Biol Reprod 1986, 34: 488–94.

    Article  PubMed  CAS  Google Scholar 

  13. Chu SC, Chou YC, Liu JY, Chen CH, Shyu JC, Chou FP. Fluctuation of serum leptin level in rats after ovariectomy and the influence of estrogen supplement. Life Sci 1999, 64: 2299–306.

    Article  PubMed  CAS  Google Scholar 

  14. Ferrer M, Osol G. Estrogen replacement modulates resistance artery smooth muscle and endothelial alpha2-adrenoceptor reactivity. Endothelium 1998, 6: 133–41.

    Article  PubMed  CAS  Google Scholar 

  15. Kau MM, Lo MJ, Tsai SC, Et Al. Effects of estradiol on al-dosterone secretion in ovariectomized rats. J Cell Biochem 1999, 73: 137–44.

    Article  PubMed  CAS  Google Scholar 

  16. Lo MJ, Kau MM, Chen JJ, Et Al. Age-related differences in corticosterone secretion in female rats. Metabolism 1999, 48: 535–41.

    Article  PubMed  CAS  Google Scholar 

  17. Gomez F, Lahmame A, De Kloet ER, Armario A. Hypothalamic-pituitary-adrenal response to chronic stress in five inbred rat strains: differential responses are mainly located at the adrenocortical level. Neuroendocrinology 1996, 63: 327–37.

    Article  PubMed  CAS  Google Scholar 

  18. Grota LJ, Bienen T, Felten DL. Corticosterone responses of adult Lewis and Fischer rats. J Neuroimmunol 1997, 74: 95–101.

    Article  PubMed  CAS  Google Scholar 

  19. Watts AG, Swanson LW. Diurnal variations in the content of preprocorticotropin-releasing hormone messenger ri-bonucleic Acids in the hypothalamic paraventricular nucleus of rats of both sexes as measured by in situ hybridization. Endocrinology 1989, 125: 1734–8.

    Article  PubMed  CAS  Google Scholar 

  20. Shakhar K, Shakhar G, Rosenne E, Ben-Eliyahu S. Timing within the menstrual cycle, sex, and the use of oral contraceptives determine adrenergic suppression of NK cell activity. Br J Cancer 2000, 83: 1630–36.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Avitsur R, Donchin O, Barak O, Cohen E, Yirmiya R. Behavioral effects of interleukin-1 beta: modulation by gender, estrus cycle, and progesterone. Brain Behav Immun 1995, 9: 234–41.

    Article  PubMed  CAS  Google Scholar 

  22. Ben-Eliyahu S. Increased susceptibility to metastasis during pro-oestrus/oestrus in rats: possible role of oestradiol and natural killer cells. Physiol Behav 1996, 60: 277–82.

    Article  PubMed  Google Scholar 

  23. Page GG, Ben-Eliyahu S. Increased surgery-induced metastasis and suppressed natural killer cell activity during proestrus/estrus in rats. Breast Cancer Res Treat 1997, 45: 159–67.

    Article  PubMed  CAS  Google Scholar 

  24. Ratajczak HV, Sothern RB, Hrushesky WJ. Estrous influence on surgical cure of a mouse breast cancer. J Exp Med 1988, 168: 73–83.

    Article  PubMed  CAS  Google Scholar 

  25. Viau V, Meaney MJ. Variations in the hypothalamic-pitu-itary-adrenal response to stress during the estrous cycle in the rat. Endocrinology 1991, 129: 2503–11.

    Article  PubMed  CAS  Google Scholar 

  26. Ben-Eliyahu S, Shakhar G, David K, Melamed R. Timing within the estrous cycle modulates adrenergic suppression of NK activity and resistance to metastasis: possible clinical im-plications (abstract). Brain Behav Immunity 2000, 14: 80–1.

    Google Scholar 

  27. Wolf DC, Goldsworthy TL, Donner EM, Harden R, Fitzpatrick B, Everitt JI. Estrogen treatment enhances hereditary renal tumor development in Eker rats. Carcinogenesis 1998, 19: 2043–7.

    Article  PubMed  CAS  Google Scholar 

  28. de Weerdt O, Gooren LJ. Patterns of serum cortisol levels in ovariectomized females with and without androgen administration. Horm Metab Res 1992, 24: 82–4.

    Article  PubMed  Google Scholar 

  29. Ogle TF, George P, Dai D. Progesterone and estrogen regulation of rat decidual cell expression of proliferating cell nuclear antigen. Biol Reprod 1998, 59: 444–50.

    Article  PubMed  CAS  Google Scholar 

  30. Longhurst PA, Kauer J, Leggett RE, Levin RM. The influence of ovariectomy and estradiol replacement on urinary bladder function in rats. J Urol 1992, 148: 915–9.

    PubMed  CAS  Google Scholar 

  31. Lhoste EF, Roebuck BD, Brinck-Johnsen T, Longnecker DS. Effect of castration and hormone replacement on azaser-ine-induced pancreatic carcinogenesis in male and female Fischer rats. Carcinogenesis 1987, 8: 699–703.

    Article  PubMed  CAS  Google Scholar 

  32. Montagne MN, Vial M, Joubert-Bression D, Rostene W. Hyperprolactinemia-induced modifications in vasoactive intestinal peptide binding site densities in the rat central nervous system and pituitary gland: evidence for an interaction between estradiol-17 beta and prolactin effects. Brain Res 1989, 485: 258–66.

    Article  PubMed  CAS  Google Scholar 

  33. Ratka A, Simpkins JW. Dose-dependent effects of chronic treatment with estradiol or progesterone on LH secretion in ovariectomized rats. Endocr Res 1990, 16: 165–84.

    Article  PubMed  CAS  Google Scholar 

  34. Redei E, Li L, Halasz I, McGivern RF, Aird F. Fast gluco-corticoid feedback inhibition of ACTH secretion in the ovariectomized rat: effect of chronic estrogen and progesterone. Neuroendocrinology 1994, 60: 113–23.

    Article  PubMed  CAS  Google Scholar 

  35. Valdes CT, Elkind-Hirsch KE, Rogers DG, Adelman JP. The hypothalamic-pituitary axis of streptozotocin-induced Diabetic female rats is not normalized by estradiol replacement. Endocrinology 1991, 128: 433–40.

    Article  PubMed  CAS  Google Scholar 

  36. Zhang Y, Davidge ST. Effect of estrogen replacement on vasoconstrictor responses in rat mesenteric Arteries. Hypertension 1999, 34: 1117–22.

    Article  PubMed  CAS  Google Scholar 

  37. Lu JK, Damassa DA, Gilman DP, Judd HL, Sawyer CH. Differential patterns of gonadotropin responses to ovarian steroids and to LH-releasing hormone between constant-estrous and pseudopregnant states in aging rats. Biol Reprod 1980, 23: 345–51.

    Article  PubMed  CAS  Google Scholar 

  38. D’Amour FE, Blood FR. Manual for laboratory work in mammalian physiology. Chicago: Chicago Press 1954.

    Google Scholar 

  39. Nequin L, Alvarez J, Schwartz N. Measurement of serum steroid and gonadotropin levels and uterine and ovarian variables throughout 4 day and 5 day estrous cycles in the rat. Biol Reprod 1979, 20: 659–70.

    Article  PubMed  CAS  Google Scholar 

  40. Lapolt P, Matt D, Judd H, Lu J. The relation of ovarian steroid levels in young female rats to subsequent estrous cyclicity and reproductive function during aging. Biol Reprod 1986, 35: 1131–9.

    Article  PubMed  CAS  Google Scholar 

  41. Smith CC, Cizza G, Gomez M, Greibler C, Gold PW, Sternberg EM. The estrous cycle and pituitary-ovarian function in Lewis and Fischer rats. Neuroimmunomodulation 1994, 1: 231–5.

    Article  PubMed  CAS  Google Scholar 

  42. Rodrigues ML, Marcondes FK, Spadari-Bratfisch RC. Relationship among sensitivity to adrenaline, plasma cor-ticosterone level, and estrous cycle in rats. Can J Physiol Pharmacol 1995, 73: 602–7.

    Article  PubMed  CAS  Google Scholar 

  43. Atkinson HC, Waddell BJ. Circadian variation in basal plasma corticosterone and adrenocorticotropin in the rat: sexual dimorphism and changes across the estrous cycle. Endocrinology 1997, 138: 3842–8.

    PubMed  CAS  Google Scholar 

  44. Chisari A, Carino M, Perone M, Gaillard RC, Spinedi E. Sex and strain variability in the rat hypothalamo-pituitary-adrenal (HPA) axis function. J Endocrinol Invest 1995, 18: 25–33.

    Article  PubMed  CAS  Google Scholar 

  45. Dhabhar FS, McEwen BS, Spencer RL. Stress response, adrenal steroid receptor levels and corticosteroid-binding globulin levels — a comparison between Sprague-Dawley, fischer 344 and Lewis rats. Brain Research 1993, 616: 89–98.

    Article  PubMed  CAS  Google Scholar 

  46. Griffin AC, Whitacre CC. Sex and strain differences in the circadian rhythm fluctuation of endocrine and immune function in the rat: implications for rodent models of autoimmune disease. J Neuroimmunol 1991, 35: 53–64.

    Article  PubMed  CAS  Google Scholar 

  47. Stohr T, Schulte Wermeling D, Szuran T, et al. Differential effects of prenatal stress in two inbred strains of rats. Pharmacol Biochem Behav 1998, 59: 799–805.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neuroimmunology Research Unit, Department of Psychology, Tel Aviv University, Tel Aviv, 69978, Israel

    S. Haim, G. Shakhar, E. Rossene &  S. Ben-Eliyahu

  2. Department of Neurobiology, University of California, Los Angeles School of Medicine and Veterans Affairs, Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles, CA, USA

    A. N. Taylor

Authors
  1. S. Haim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Shakhar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Rossene
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. N. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Ben-Eliyahu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Ben-Eliyahu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Haim, S., Shakhar, G., Rossene, E. et al. Serum levels of sex hormones and corticosterone throughout 4- and 5-day estrous cycles in Fischer 344 rats and their simulation in ovariectomized females. J Endocrinol Invest 26, 1013–1022 (2003). https://doi.org/10.1007/BF03348201

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03348201

Key-words

Search

Navigation