Stress and the developing limbic-hypothalamic-pituitary-adrenal axis. 1998

D M Vázquez
Mental Health Research Institute, University of Michigan, Ann Arbor 48109-0646, USA. dmVazq@umich.edu

The postnatal limbic-hypothalamic-pituitary-adrenal (LHPA) axis in the rodent is remarkably different from the adult, both in structure and function. The first 2 weeks postnatally are characterized by a 'silent period' during which the developing animal is hyporesponsive to stress (stress hyporesponsive period-SHRP), followed by a new and unique phase of stress responsiveness when the animal fails to swiftly terminate glucocorticoid secretion. In this review, we summarize our work which focuses on the regulatory biology of the components of the LHPA system and the consequences of its disruption on the adaptive responses of the developing organism. We find that the animal during the first 2 weeks of life responds to an intermittent chronic challenge increasing anterior pituitary POMC post-translational events, while the adult increases genomic events. The result for both the mature and the developing animal is the same, an increase in corticosterone (CS) levels. In addition, we have found evidence of impaired rate sensitive feedback in the weanling animal, as well as changes in ACTH clearance. Similar to the young animal emerging from SHRP, maternally deprived pups during the first week of life exhibit a substantial and sustained ACTH and CS response to stress. In the deprived animal these changes are accompanied by decreases in mineralocorticoid receptor gene expression in the hippocampus, suggesting that changes in mineralocorticoid to glucocorticoid receptor ratios may be important in this phenomena. What has become evident from our studies is that mechanisms underlying normal LHPA development are dynamic, age dependent and distinct to the strategies used by the mature organism to cope with stress.

UI MeSH Term Description Entries
D007030 Hypothalamo-Hypophyseal System A collection of NEURONS, tracts of NERVE FIBERS, endocrine tissue, and blood vessels in the HYPOTHALAMUS and the PITUITARY GLAND. This hypothalamo-hypophyseal portal circulation provides the mechanism for hypothalamic neuroendocrine (HYPOTHALAMIC HORMONES) regulation of pituitary function and the release of various PITUITARY HORMONES into the systemic circulation to maintain HOMEOSTASIS. Hypothalamic Hypophyseal System,Hypothalamo-Pituitary-Adrenal Axis,Hypophyseal Portal System,Hypothalamic-Pituitary Unit,Hypothalamic Hypophyseal Systems,Hypothalamic Pituitary Unit,Hypothalamo Hypophyseal System,Hypothalamo Pituitary Adrenal Axis,Portal System, Hypophyseal
D008032 Limbic System A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the AMYGDALA; EPITHALAMUS; GYRUS CINGULI; hippocampal formation (see HIPPOCAMPUS); HYPOTHALAMUS; PARAHIPPOCAMPAL GYRUS; SEPTAL NUCLEI; anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). Limbic Systems,System, Limbic,Systems, Limbic
D008426 Maternal Deprivation Prolonged separation of the offspring from the mother. Deprivation, Maternal,Deprivations, Maternal,Maternal Deprivations
D010913 Pituitary-Adrenal System The interactions between the anterior pituitary and adrenal glands, in which corticotropin (ACTH) stimulates the adrenal cortex and adrenal cortical hormones suppress the production of corticotropin by the anterior pituitary. Pituitary Adrenal System,Pituitary-Adrenal Systems,System, Pituitary-Adrenal,Systems, Pituitary-Adrenal
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011333 Pro-Opiomelanocortin A 30-kDa protein synthesized primarily in the ANTERIOR PITUITARY GLAND and the HYPOTHALAMUS. It is also found in the skin and other peripheral tissues. Depending on species and tissues, POMC is cleaved by PROHORMONE CONVERTASES yielding various active peptides including ACTH; BETA-LIPOTROPIN; ENDORPHINS; MELANOCYTE-STIMULATING HORMONES; and others (GAMMA-LPH; CORTICOTROPIN-LIKE INTERMEDIATE LOBE PEPTIDE; N-terminal peptide of POMC or NPP). POMC,Pro-Opiocortin,ACTH-Endorphin Precursor,ACTH-beta-Lipotropin Precursor,Corticotropin-beta-Lipotropin Precursor,Endorphin-ACTH Precursor,Opiocortin,Pre-POMC,Pre-pro-opiocortin,Preproopiomelanocortin,Pro-ACTH-Endorphin,Pro-Opio-Melanocortin,Proopiocortin,Proopiomelanocortin,ACTH Endorphin Precursor,ACTH beta Lipotropin Precursor,Corticotropin beta Lipotropin Precursor,Endorphin ACTH Precursor,Pre POMC,Pre pro opiocortin,Pro ACTH Endorphin,Pro Opio Melanocortin,Pro Opiocortin,Pro Opiomelanocortin
D001931 Brain Mapping Imaging techniques used to colocalize sites of brain functions or physiological activity with brain structures. Brain Electrical Activity Mapping,Functional Cerebral Localization,Topographic Brain Mapping,Brain Mapping, Topographic,Functional Cerebral Localizations,Mapping, Brain,Mapping, Topographic Brain
D003345 Corticosterone An adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. (From Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1437)
D005246 Feedback A mechanism of communication within a system in that the input signal generates an output response which returns to influence the continued activity or productivity of that system. Feedbacks
D005260 Female Females

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