       Document 0694
 DOCN  M9640694
 TI    Effects of short-term dexamethasone treatment during pregnancy on the
       development of the immune system and the hypothalamo-pituitary adrenal
       axis in the rat.
 DT    9604
 AU    Bakker JM; Schmidt ED; Kroes H; Kavelaars A; Heijnen CJ; Tilders FJ; van
       Rees EP; Department of Cell Biology and Immunology, Faculty of
       Medicine,; Vrije Universiteit, Amsterdam, Netherlands.
 SO    J Neuroimmunol. 1995 Dec 31;63(2):183-91. Unique Identifier : AIDSLINE
       MED/96133578
 AB    The effects of glucocorticoid (GC) treatment on the mature immune and
       neuroendocrine system are known to be reversible. However, prenatal GC
       exposure may have irreversible consequences on the development of the
       newborn. In this study, possible long-lasting effects of short-term
       prenatal GC treatment were examined on the developing thymus, spleen and
       hypothalamo-pituitary adrenal axis (HPA axis). Female rats were given
       dexamethasone (DEX, 400 micrograms, i.p.) on day 17 and 19 of pregnancy
       and offspring was studied at several time intervals (1-20 days) after
       birth, for examination of thymus, spleen, hypothalamus and blood plasma.
       Examination of thymus and spleen revealed that prenatal exposure to DEX
       resulted in decreased T cell numbers in thymus and spleen on day 1 after
       birth. Thymus regeneration after DEX exposure both during pregnancy and
       in adult life was completed after 24 days. However, the kinetics of
       regeneration of the thymi after prenatal DEX exposure were different
       from that seen after DEX in adult life. Whereas DEX treatment during
       pregnancy resulted in an increased ratio of CD4+/CD8- thymocytes over
       CD4-/CD8+ thymocytes compared to control groups on day 7 and day 20
       after birth (time X treatment interaction; P < 0.05), DEX treatment in
       adult life did not change this ratio. T cell numbers in the spleen were
       significantly decreased at all neonatal ages studied. Regarding the
       hypothalamus, prenatal exposure to DEX altered the pattern of neonatal
       changes in peptide expression in corticotropin-releasing hormone
       neurons, with a selective reduction in CRH storage in the median
       eminence (7 and 9 days after birth) and an increase in AVP storage (9
       and 20 days after birth). The ratio of AVP over CRH was significantly
       increased at all developmental ages studied. No effects were seen on
       basal ACTH and corticosterone levels in plasma. In conclusion, the
       kinetics of thymus regeneration after DEX exposure during pregnancy were
       different from that seen after DEX exposure in adult life. Prenatal DEX
       exposure also seemed to delay the migration of T cells into the spleen.
       Furthermore, prenatal DEX treatment exerted major effects on
       hypothalamic CRH neurons that maintained for at least 20 days after
       birth, which points towards an enhanced stress responsiveness of the HPA
       axis in later life.
 DE    Animal  Corticosterone/BLOOD  Corticotropin/BLOOD
       Corticotropin-Releasing Hormone/SECRETION  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY/ULTRASTRUCTURE  CD8-Positive
       T-Lymphocytes/IMMUNOLOGY/ULTRASTRUCTURE  Dexamethasone/*PHARMACOLOGY
       Female  Hypothalamo-Hypophyseal System/*EMBRYOLOGY/*IMMUNOLOGY
       Hypothalamus/CYTOLOGY/IMMUNOLOGY/ULTRASTRUCTURE  Immune System/*DRUG
       EFFECTS/*EMBRYOLOGY/IMMUNOLOGY  Immunophenotyping  Male  Pregnancy
       Prenatal Exposure Delayed Effects  Rats  Rats, Wistar  Receptors,
       Antigen, T-Cell, alpha-beta/IMMUNOLOGY  Spleen/CYTOLOGY/IMMUNOLOGY
       Support, Non-U.S. Gov't  T-Lymphocyte Subsets/IMMUNOLOGY/ULTRASTRUCTURE
       Thymus Gland/CYTOLOGY/IMMUNOLOGY  Time Factors  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

