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Attenuation of hypothalamic-pituitary-adrenal axis stress responses in late pregnancy: changes in feedforward and feedback mechanisms.
J Neuroendocrinol. 2000 Aug; 12(8):811-22.JN

Abstract

The 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, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-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 11beta-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 11beta-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.

Authors+Show Affiliations

Departments of Biomedical Sciences and Molecular Endocrinology, University of Edinburgh, Edinburgh, UK. Max Planck Institute of Psychiatry, Munich, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10929094

Citation

Johnstone, H A., et al. "Attenuation of Hypothalamic-pituitary-adrenal Axis Stress Responses in Late Pregnancy: Changes in Feedforward and Feedback Mechanisms." Journal of Neuroendocrinology, vol. 12, no. 8, 2000, pp. 811-22.
Johnstone HA, Wigger A, Douglas AJ, et al. Attenuation of hypothalamic-pituitary-adrenal axis stress responses in late pregnancy: changes in feedforward and feedback mechanisms. J Neuroendocrinol. 2000;12(8):811-22.
Johnstone, H. A., Wigger, A., Douglas, A. J., Neumann, I. D., Landgraf, R., Seckl, J. R., & Russell, J. A. (2000). Attenuation of hypothalamic-pituitary-adrenal axis stress responses in late pregnancy: changes in feedforward and feedback mechanisms. Journal of Neuroendocrinology, 12(8), 811-22.
Johnstone HA, et al. Attenuation of Hypothalamic-pituitary-adrenal Axis Stress Responses in Late Pregnancy: Changes in Feedforward and Feedback Mechanisms. J Neuroendocrinol. 2000;12(8):811-22. PubMed PMID: 10929094.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Attenuation of hypothalamic-pituitary-adrenal axis stress responses in late pregnancy: changes in feedforward and feedback mechanisms. AU - Johnstone,H A, AU - Wigger,A, AU - Douglas,A J, AU - Neumann,I D, AU - Landgraf,R, AU - Seckl,J R, AU - Russell,J A, PY - 2000/8/6/pubmed PY - 2000/9/9/medline PY - 2000/8/6/entrez SP - 811 EP - 22 JF - Journal of neuroendocrinology JO - J. Neuroendocrinol. VL - 12 IS - 8 N2 - The 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, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-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 11beta-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 11beta-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. SN - 0953-8194 UR - https://www.unboundmedicine.com/medline/citation/10929094/Attenuation_of_hypothalamic_pituitary_adrenal_axis_stress_responses_in_late_pregnancy:_changes_in_feedforward_and_feedback_mechanisms_ L2 - https://doi.org/10.1046/j.1365-2826.2000.00525.x DB - PRIME DP - Unbound Medicine ER -