Attenuation of Hypothalamic‐Pituitary‐Adrenal Axis Stress Responses in Late Pregnancy: Changes in Feedforward and Feedback Mechanisms

Journal of Neuroendocrinology - Tập 12 Số 8 - Trang 811-822 - 2000
Heather A. Johnstone1,2, Alexandra Wigger3, Alison J. Douglas1, Inga D. Neumann3, Rainer Landgraf3, Jonathan R. Seckl2, John A. Russell1
1Departments of Biomedical Sciences and
2Molecular Endocrinology, University of Edinburgh, Edinburgh, UK.
3Max Planck Institute of Psychiatry, Munich, Germany

Tóm tắt

AbstractThe hypothalamic‐pituitary‐adrenal axis is hyporesponsive to stress in late pregnancy, exemplified as reduced adrenocorticotropic hormone (ACTH) and corticosterone responses to restraint, but the mechanisms are unknown. We investigated forward drive and negative feedback upon the hypothalamic‐pituitary‐adrenal axis in pregnant rats. Corticotropin‐releasing hormone (CRH) and vasopressin mRNA expression in the parvocellular paraventricular nucleus and mineralocorticoid and glucocorticoid receptor expression in the paraventricular nucleus and hippocampus were quantified with in situ hybridization. Because it can enhance the corticosterone negative feedback signal, 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) bioactivity in these brain regions and anterior pituitary was measured in vitro, and ACTH and corticosterone stress responses were measured after intracerebroventricular glycyrrhetinic acid, an 11β‐HSD inhibitor. Changes in corticosterone feedback on ACTH secretion were examined after pharmacological adrenalectomy by metyrapone and aminoglutethimide. Parvocellular paraventricular nucleus CRH mRNA content was reduced on day 21 and the CRH mRNA : vasopressin mRNA ratio was unaltered, indicating decreased production of both CRH and vasopressin. An increase in glucocorticoid receptor mRNA expression in the dentate gyrus (mineralocorticoid receptor mRNA expression was unaltered) and increased 11β‐HSD1 activity in the paraventricular nucleus and anterior pituitary suggest an increase in slow negative feedback mechanisms in pregnancy, but glycyrrhetinic acid did not modify the stress response. After metyrapone/aminoglutethimide treatment, corticosterone decreased ACTH secretion more slowly in pregnancy, indicating a decrease in rapid feedback sensitivity. Thus, reduced forward drive rather than increased effectiveness of glucocorticoid negative feedback may underlie stress hyporesponsiveness of the hypothalamic‐pituitary‐adrenal axis in pregnancy.

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Tài liệu tham khảo

10.1210/endo.136.2.7835284

10.1210/jc.80.10.2954

10.1046/j.1365-2826.1997.00587.x

10.1111/j.1469-7793.1998.289br.x

Douglas AJ, 1994, Corticotrophin‐releasing hormone, proenkephalin A and oxytocin mRNAs in the paraventricular nucleus during pregnancy and parturition in the rat, Gene Ther, 1, S85

10.1016/S0006-8993(96)00962-6

10.1210/jcem-29-3-352

10.1210/endo-116-2-552

10.1006/frne.1996.0143

10.1210/endo-127-3-1450

10.1111/j.1365-2826.1992.tb00351.x

10.1523/JNEUROSCI.16-01-00065.1996

10.1111/j.1365-2826.1990.tb00659.x

10.1210/endo-129-6-3118

10.1677/joe.0.1360471

10.1016/0960-0760(93)90296-9

Cohen A, 1990, Effect of adrenalectomy at different pregnancy stages on maternal and fetal serum corticosteroid binding globulin and corticosterone in the rat, Acta Endocrinol, 122, 121

10.1210/endo-120-4-1361

10.1042/bj2180703

10.1677/joe.0.1580285

10.1159/000124910

Jones CT, 1989, Production of corticotrophin releasing hormone by the sheep placenta in vivo, J Dev Physiol, 11, 97

10.1016/0303-7207(89)90022-1

10.1210/endo-118-6-2382

10.1677/joe.0.1430183

10.1210/endo-129-5-2503

10.1210/endo-77-5-902

10.1111/j.1365-2826.1996.tb00830.x

10.1016/0006-8993(92)91680-D

10.1002/cne.903320102

10.1210/endo-117-6-2505

10.1073/pnas.81.6.1883

10.1159/000124650

10.1016/0169-328X(94)90083-3

10.1210/endo-117-5-1803

10.1111/j.1365-2826.1994.tb00604.x

10.1016/0306-4522(94)00407-V

10.1016/0031-9384(89)90187-X

10.1042/bst0270078

10.1210/mend-3-11-1886

10.1210/endo.132.6.8504762

10.1016/S0169-328X(98)00161-2

10.1073/pnas.94.26.14924

10.1210/me.6.7.1082

10.1111/j.1365-2826.1994.tb00584.x

10.1677/joe.0.1390027

Armanini D, 1985, Binding of agonists and antagonists to mineralocorticoid receptors in human peripheral mononuclear leucocytes, J Hypertension, 3, S157

10.1016/0024-3205(87)90603-5

Keller‐Wood M, 1996, Inhibition of stimulated and basal ACTH by cortisol during ovine pregnancy, Am J Physiol, 271, R130

10.1159/000127146

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Thông tin xuất bản

Journal of Neuroendocrinology

Tập 12 Số 8

811-822

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