Modified Development of the Hypothalamo-Pituitary-Adrenocortical (HPA) Axis Response to Stress in Young Rodents with Experimentally Altered Thyroid Status

  • Lee A. Meserve
Part of the Biochemical Endocrinology book series (BIOEND)


The study of development of the stress-adaptive hypothalamo-pituitary-adrenocortical (HPA) axis in young rodents is of interest because of the considerable degree of maturation which occurs postnatally. When first described by Schapiro et al. (1962), the so-called stress non-responsive (SNR) period was felt to be absolute, with the HPA axis of rats unable to respond to a stress between approximately postnatal days 3 and 12. With the advancement of technological methods it has been demonstrated that the SNR period is relative rather than absolute, and that HPA axis response during this time is dampened rather than prevented (Schoenfeld et al., 1980; Milkovic et al., 1982). Nonetheless, significant maturation of HPA axis components must occur before response levels approach those of adults, after the third postnatal week (Guillet et al., 1980).


Congenital Hypothyroidism Thyroid Status Axis Response Zona Fasciculata Cell Hypothyroid Mouse 
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  1. Angwin, P., and Barchas, J.D., 1982. Analysis of peptides in tissues and plasma: use of silicic acid extraction and reverse-phase columns for rapid purification prior to radioimmunoassay, J. Chromatogr., 231: 173–177.PubMedCrossRefGoogle Scholar
  2. Beamer, W.G., and Cresswell, L.A., 1982, Defective thyroid ontogenesis in fetal hypothyroid (hyt/hyt) mice, Anat. Rec., 202: 387–393.PubMedCrossRefGoogle Scholar
  3. Beamer, W.G., Eicher, E.M., Maltais, L.J., and Southard, J.L., 1981, Inherited primary hypothyroidism in mice, Science, 212: 61–63.PubMedCrossRefGoogle Scholar
  4. Callas, G., 1971, Changes in the fine structure of the adrenal cortex in the albino rat following the administration of propylthiouracil, Anat. Rec., 169: 474.Google Scholar
  5. Colby, H.D., Caffrey, J.H., and Kitay, J.I., 1973, Interaction of growth hormone and ACTH in the regulation of adrenocortical secretion in rats, Endocrinology, 93: 188–192.PubMedCrossRefGoogle Scholar
  6. Davenport, G.R., and Mallette, L.E., 1966, Some biochemical properties of rabbit ovarian hydroxysteroid dehydrogenases, Endocrinology, 78: 672–678.PubMedCrossRefGoogle Scholar
  7. Eayrs, J.T., 1964, Effect of neonatal hyperthyroidism on maturation and learning in the rat, Anim. Behav., 12: 195–199.CrossRefGoogle Scholar
  8. Froelich, P.A., and Meserve, L.A., 1982, Altered growth patterns and depressed pituitary growth hormone content in young rats: effects of pre- and postnatal thiouracil administration, Growth, 46: 296–305.PubMedGoogle Scholar
  9. Glick, D., von Redlich, D., and Levine, S., 1964, Fluorometric determination of corticosterone and Cortisol in 0.02–0.05 milliliters of plasma or submilligram samples of adrenal tissue, Endocrinology, 74: 653–655.PubMedCrossRefGoogle Scholar
  10. Greenberg, A.M., Naijar, S., and Blizzard, R.M., 1974, Effects of thyroid hormone on growth, differentiation, and development, in “Handbook of Physiology, Endocrinology, Thyroid”, M.A. Greer and D.H. Solomon, eds., American Physiological Society, Washington, D.C., USA.Google Scholar
  11. Guillet, R., Saffran, M., and Michaelson, S.M., 1980, Pituitary-adrenal response in neonatal rats, Endocrinology, 106: 991–994.PubMedCrossRefGoogle Scholar
  12. Hilf, R., Burnett, F.F., and Borman, A., 1960, The effect of sarcoma 180 and other stressing agents upon adrenal and plasma corticosterone in mice, Cancer Res., 20: 1389–1393.PubMedGoogle Scholar
  13. Kitay, J.I., Coyne, M.D., and Swygert, N.H., 1970, Influence of gonadectomy and replacement with estradiol or testosterone on formation of 5α-reduced metabolites of corticosterone by the adrenal gland of the rat, Endocrinology, 87: 1257–1265.PubMedCrossRefGoogle Scholar
  14. Klak, A.T., and Meserve, L.A., 1983, Effects of thiouracil-induced hypothyroidism on adrenal ultrastructure, Micron Microsc. Acta, 14: 275–276.CrossRefGoogle Scholar
  15. Larsen, P.R., 1980, Hypothyroidism: a common endocrine disease in all age groups, Med. Times, 108: 47–60.PubMedGoogle Scholar
  16. Meserve, L.A., 1976, The influence of thiouracil-induced hypothyroidism upon hypothalamo-hypophyseal-adrenal axis response in the 15 day old mouse, Sci. Biol. J., 2: 200–206.Google Scholar
  17. Meserve, L.A., 1984, Depressed hypothalamic CRF immunoreactivity in 15 day old thiouracil-treated rats, Hormone Metab. Res., In press.Google Scholar
  18. Meserve, L.A., and Leathern, J.H., 1973, Hypothyroidism and the maturation of the hypothalamo-hypophyseal-adrenal axis, Develop. Psycholbiol., 6: 123–129.CrossRefGoogle Scholar
  19. Meserve, L.A., and Leathern, J.H., 1974, Neonatal hyperthyroidism and maturation of the rat hypothalamo-hypophyseal-adrenal axis, Proc. Soc. Exp. Biol. Med., 147: 510–512.PubMedGoogle Scholar
  20. Meserve, L.A., and Leathern, J.H., 1981, Development of hypothalamic-pituitary-adrenal response to stress in rats made hypothyroid by exposure to thiouracil from conception, J. Endocrinol., 90: 403–409.PubMedCrossRefGoogle Scholar
  21. Meserve, L.A., and Pearlmutter, A.F., 1983, Perinatal thiouracil exposure depresses corticotropin-releasing factor activity in 15 day old rats, Hormone Metab. Res. 15: 488–490.CrossRefGoogle Scholar
  22. Meserve, L.A., and Rahman, Z.-U., 1984, Adrenal 5a-reductase activity in normal male and female and thiouracil fed male mice, Ohio J. Sci. 84: 28.Google Scholar
  23. Meserve, L.A., and Rhodes, A.B., 1979, Influence of pre- and postnatal thiouracil on pituitary growth hormone content in mice, Ohio J. Sci., 79: 267–271.Google Scholar
  24. Meserve, L.A., and Scriffignano, J.S., 1984, Thyroid feeding from conception and hypothalamo-pituitary-adrenal axis response in 30 day old rats, Ohio J. Sci., In press.Google Scholar
  25. Meserve, L.A., and Ting, S.-M., 1982, Response of adrenal 3β-hydroxy-Δ5-steroid dehydrogenase to adrenocorticotropin treatment in thiouracil-fed male mice, Can. J. Physiol. Pharmacol., 60: 83–87.PubMedCrossRefGoogle Scholar
  26. Milković, K., Peruzović, M., and Paunović, J., 1982, Pituitary and adrenal glands in neonatal rats studied by metopirone (SU 4885), Biol. Neonate. 41: 32–37.PubMedCrossRefGoogle Scholar
  27. Noguchi, T., and Sugisaki, T., 1984, Hypomyelination in the cerebrum of the congenitally hypothyroid mouse (hyt), J. Neurochem., 42: 891–893.PubMedCrossRefGoogle Scholar
  28. Nussdorfer, G.G., Meneghelli, V., and Mazzocchi, G., 1984, Fine structure of the adenal cortex, in: “Ultrastructure of Endocrine Cells and Tissues”, P.M. Motta, ed., Martinus Nijhoff Publishers, The Hague, Netherlands.Google Scholar
  29. Oppenheimer, J.H., Schwartz, H.L., and Surks, M.I., 1972, Propylthiouracil inhibits the conversion of L-thyroxine to L-triiodothyronine. An explanation of the antithyroid effect of propylthiouracil and evidence supporting the concept that triiodothyronine is the active thyroid hormone, J. Clin. Invest., 51: 2493–2497.PubMedCrossRefGoogle Scholar
  30. Pearlmutter, A.F., Rapino, E., and Saffran, M., 1974, A semi-automated in vitro assay for CRF: activities of peptides related to oxytocin and vasopressin, Neuroendocrinology, 15: 106–119.PubMedCrossRefGoogle Scholar
  31. Pelton, E.W., and Bass, N.H., 1973, Adverse effects of excess thyroid hormone on the maturation of the rat cerebrum, Arch. Neurol., 29: 145–150.CrossRefGoogle Scholar
  32. Poland, R.E., Weichsel, Jr., M.E., and Rubin, R.T., 1979, Postnatal maturation patterns of serum corticosterone and growth hormone in rats: effect of chronic thyroxine administration, Hormone Metab. Res., 11: 222–227.CrossRefGoogle Scholar
  33. Rivier, J., Spiess, J., and Vale, W., 1983, Characterization of rat hypothalamic corticotropin-releasing factor, Proc. Natl. Acad. Sci. USA, 80: 4851–4856.PubMedCrossRefGoogle Scholar
  34. Saffran, M., Matthews, E.K., and Pearlmutter, A.F., 1971, Analysis of the response to ACTH by rat adrenal in a flowing system, Recent Prog. Hormone Res., 27: 607–630.Google Scholar
  35. Schapiro, S., Geller, E., and Eiduson, W., 1962, Neonatal adrenocortical response to stress and vasopressin, Proc. Soc. Exp. Biol. Med., 109: 937–941.PubMedGoogle Scholar
  36. Schoenfeld, N.M., Leathern, J.H., and Rabii, J., 1980. Maturation of adrenal stress responsiveness in the rat, Neuroendocrinology, 31: 101–105.PubMedCrossRefGoogle Scholar
  37. Schulte, D., 1980, Effect of hypothyroidism on adrenal ultrastructure in stressed and unstressed young rats, Ohio J. Sci., 80: 12.Google Scholar
  38. Shire, J.G.M., and Beamer, W.G., 1984, Adrenal changes in genetically hypothryoid mice, J. Endocrinol. 102: 277–280.PubMedCrossRefGoogle Scholar
  39. Steinetz, B.G., and Beach, V.L., 1963, Some influences of thyroid on the pituitary adrenal axis, Endocrinology, 72: 45–58.PubMedCrossRefGoogle Scholar
  40. Taurog, A., 1976, The mechanism of action of the thioureylene antithyroid drugs, Endocrinology, 98: 1031–1046.PubMedCrossRefGoogle Scholar
  41. Vanderpas, J., Bordoux, P., Lagasse, R., Rivera, M., Dramaix, M., Lody, D., Nelson, G., Delange, F., Ermans, A.M., and Thilly, C.H., 1984, Endemic infantile hypothyroidism in a severe endemic goitre area of central Africa, Clin. Endocrinol., 20: 327–340.Google Scholar
  42. Weibel, E.R., Kistler, G.S., and Scherle, W.F., 1966, Practical stereological methods for morphometric cytology, J. Cell Biol. 30: 23–38.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Lee A. Meserve
    • 1
  1. 1.Department of Biological SciencesBowling Green State UniversityBowling GreenUSA

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