Prenatal stress alters circadian activity of hypothalamo-pituitary-adrenal axis and hippocampal corticosteroid receptors in adult rats of both gender.

Prenatal stress impairs activity of the hypothalamo-pituitary-adrenal (HPA) axis in response to stress in adult offspring. So far, very few data are available on the effects of prenatal stress on circadian functioning of the HPA axis. Here, we studied the effects of prenatal stress on the circadian rhythm of corticosterone secretion in male and female adult rats. To evaluate the effects of prenatal stress on various regulatory components of corticosterone secretion, we also assessed the diurnal fluctuation of adrenocorticotropin, total and free corticosterone levels, and hippocampal corticosteroid receptors. Finally, in the search of possible maternal factors, we studied the effects of repeated restraint stress on the pattern of corticosterone secretion in pregnant female rats. Results demonstrate that prenatal stress induced higher levels of total and free corticosterone secretion at the end of the light period in both males and females, and hypercorticism over the entire diurnal cycle in females. No diurnal fluctuation of adrenocorticotropin was observed in any group studied. The effects of prenatal stress on corticosterone secretion could be mediated, at least in part, by a reduction in corticosteroid receptors at specific times of day. Results also show that prepartal stress alters the pattern of corticosterone secretion in pregnant females. Those data indicate that prenatally stressed rats exhibit an altered temporal functioning of the HPA axis, which, taken together with their abnormal response to stress, reinforces the idea of a general homeostatic dysfunction in those animals.

[1]  J. Nurnberger,et al.  Is cholinergic sensitivity a genetic marker for the affective disorders? , 1994, American journal of medical genetics.

[2]  M. Weinstock,et al.  Prenatal stress increases anxiety related behavior and alters cerebral lateralization of dopamine activity. , 1988, Life sciences.

[3]  M. Byrne,et al.  Nocturnal exercise phase delays circadian rhythms of melatonin and thyrotropin secretion in normal men. , 1994, The American journal of physiology.

[4]  C. Nemeroff.  The Role of Corticotropin-Releasing Factor in the Pathogenesis of Major Depression , 1988, Pharmacopsychiatry.

[5]  P. Piazza,et al.  Noradrenergic regulation of type-I and type-II corticosteroid receptors in amygdala and hypothalamus , 1992, Brain Research.

[6]  A. Mason,et al.  Central hypogonadism in burned men. , 1987, Hormone research.

[7]  J. Amsterdam,et al.  Cosyntropin (ACTH alpha 1-24) stimulation test in depressed patients and healthy subjects. , 1983, The American journal of psychiatry.

[8]  J. Hubbard,et al.  Development of an exchange assay for cytosolic glucocorticoid receptors using the synergistic effects of molybdate plus dithiothreitol. , 1983, Endocrinology.

[9]  E. D. Kloet,et al.  Feedback action and tonic influence of corticosteroids on brain function: A concept arising from the heterogeneity of brain receptor systems , 1987, Psychoneuroendocrinology.

[10]  J. Calabrese,et al.  Responses to corticotropin-releasing hormone in the hypercortisolism of depression and Cushing's disease. Pathophysiologic and diagnostic implications. , 1986, The New England journal of medicine.

[11]  I. Zucker,et al.  Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[12]  M. Meaney,et al.  Stress-induced occupancy and translocation of hippocampal glucocorticoid receptors , 1988, Brain Research.

[13]  K. Honma,et al.  Ontogeny of the circadian rhythm of plasma corticosterone in blind infantile rats. , 1982, The Journal of physiology.

[14]  M. Le Moal,et al.  Corticosterone levels determine individual vulnerability to amphetamine self-administration. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R. Frairia,et al.  Influence of Naturally Occurring and Synthetic Glucocorticoids on Corticosteroid‐Binding Globulin‐Steroid Interaction in Human Peripheral Plasma , 1988, Annals of the New York Academy of Sciences.

[16]  M. Meaney,et al.  Hypothalamic-pituitary-adrenal activity during chronic central administration of interleukin-2. , 1994, Endocrinology.

[17]  B. McEwen,et al.  Prenatal stress selectively alters the reactivity of the hypothalamic-pituitary adrenal system in the female rat , 1992, Brain Research.

[18]  M. Moal,et al.  Prenatal stress induces a phase advance of circadian corticosterone rhythm in adult rats which is prevented by postnatal stress , 1997, Brain Research.

[19]  M. Kabbaj,et al.  Hippocampal type I and TYPE II corticosteroid receptors are differentially regulated by chronic prazosin treatment , 1996, Neuroscience.

[20]  F. Turek,et al.  The effects of short periods of immobilization on the hamster circadian clock , 1991, Brain Research.

[21]  N. Kalin,et al.  Early developmental and temporal characteristics of stress-induced secretion of pituitary-adrenal hormones in prenatally stressed rat pups , 1991, Brain Research.

[22]  M. Le Moal,et al.  Maternal Glucocorticoid Secretion Mediates Long-Term Effects of Prenatal Stress , 1996, The Journal of Neuroscience.

[23]  R. Binnekade,et al.  Diurnal variation in resting levels of corticosterone is not mediated by variation in adrenal responsiveness to adrenocorticotropin but involves splanchnic nerve integrity. , 1996, Endocrinology.

[24]  G. Raisman,et al.  The ‘suprachiasmatic syndrome’: endocrine and behavioural abnormalities following lesions of the suprachiasmatic nuclei in the female rat , 1977, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[25]  P. Piazza,et al.  Opposite effects on hippocampal corticosteroid receptors induced by stimulation of β and α1 noradrenergic receptors , 1995, Neuroscience.

[26]  R. Moore,et al.  Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. , 1972, Brain research.

[27]  M. Huttunen.  Persistent Alteration of Turnover of Brain Noradrenaline in the Offspring of Rats subjected to Stress during Pregnancy , 1971, Nature.

[28]  P. Piazza,et al.  Hippocampal type I and type II corticosteroid receptors are modulated by central noradrenergic systems , 1992, Psychoneuroendocrinology.

[29]  M. Dallman,et al.  Roles of type I and II corticosteroid receptors in regulation of basal activity in the hypothalamo-pituitary-adrenal axis during the diurnal trough and the peak: evidence for a nonadditive effect of combined receptor occupation. , 1994, Endocrinology.

[30]  F. Holsboer,et al.  Blunted corticotropin and normal cortisol response to human corticotropin-releasing factor in depression. , 1984, The New England journal of medicine.

[31]  N. Kalin,et al.  PROLONGED STRESS-INDUCED ELEVATION IN PLASMA CORTICOSTERONE DURING PREGNANCY IN THE RAT: IMPLICATIONS FOR PRENATAL STRESS STUDIES , 1998, Psychoneuroendocrinology.

[32]  J. Baxter,et al.  Glucocorticoid hormone action: an overview. , 1979, Monographs on endocrinology.

[33]  M. Oitzl,et al.  Chronic brain glucocorticoid receptor blockade enhances the rise in circadian and stress-induced pituitary-adrenal activity. , 1996, Endocrinology.

[34]  L. Schell,et al.  Environmental noise and human prenatal growth. , 1981, American journal of physical anthropology.

[35]  Hervé Rix,et al.  Effect of recovery on the cortisol circadian rhythm of depressed patients , 1988, Biological Psychiatry.

[36]  B. McEwen,et al.  Adrenal steroid receptors and actions in the nervous system. , 1986, Physiological reviews.

[37]  M. Dallman,et al.  Daily rhythms in adrenal responsiveness to adrenocorticotropin are determined primarily by the time of feeding in the rat. , 1979, Endocrinology.

[38]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[39]  Influence of Prenatal Maternal Anxiety on Emotionality in Young Rats , 1957 .

[40]  J. Feldon,et al.  Effects of prenatal stress on vulnerability to stress in prepubertal and adult rats , 1986, Physiology & Behavior.

[41]  D. H. Stott.  Follow‐up Study from Birth of the Effects of Prenatal Stresses , 1973, Developmental medicine and child neurology.

[42]  A. Meijer.  Child psychiatric sequelae of maternal war stress , 1985, Acta psychiatrica Scandinavica.

[43]  K. Honma,et al.  Possible zeitgebers for external entrainment of the circadian rhythm of plasma corticosterone in blind infantile rats. , 1982, The Journal of physiology.

[44]  E. Navarro,et al.  Motor Lateralization, Behavioral Despair and Dopaminergic Brain Asymmetry After Prenatal Stress , 1997, Pharmacology Biochemistry and Behavior.

[45]  S. Alonso,et al.  Sex differences in behavioral despair: Relationships between behavioral despair and open field activity , 1991, Physiology & Behavior.

[46]  W. Pardridge,et al.  Protein-bound corticosteroid in human serum is selectively transported into rat brain and liver in vivo. , 1983, The Journal of clinical endocrinology and metabolism.

[47]  R. Roth,et al.  Relationships between behavioral rhythms, plasma corticosterone and hypothalamic circadian rhythms. , 1986, Chronobiology international.

[48]  C. Kilts,et al.  Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. , 1984, Science.

[49]  M. Dallman,et al.  Stress-induced adrenocorticotropin secretion: diurnal responses and decreases during stress in the evening are not dependent on corticosterone. , 1991, Endocrinology.

[50]  Aviva Wakshlak,et al.  Neonatal handling reverses behavioral abnormalities induced in rats by prenatal stress , 1990, Physiology & Behavior.

[51]  A. Armario,et al.  Direct evidence for chronic stress-induced facilitation of the adrenocorticotropin response to a novel acute stressor. , 1994, Neuroendocrinology.

[52]  M. Dallman,et al.  Nycthemeral rhythm in adrenal responsiveness to ACTH. , 1978, The American journal of physiology.

[53]  B. McEwen,et al.  Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[54]  A. Wirz-Justice,et al.  Circadian Rhythm Mechanisms in Affective Illness and in Antidepressant Drug Action , 1982, Pharmacopsychiatria.

[55]  R. J. Neufeld.  Psychological stress and psychopathology , 1982 .

[56]  P. Piazza,et al.  The mesolimbic dopaminergic system exerts an inhibitory influence on brain corticosteroid receptor affinities , 1993, Neuroscience.

[57]  B. McEwen,et al.  The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. , 1986, Endocrine reviews.

[58]  Maternal coordination of the fetal biological clock in utero. , 1983 .

[59]  B. McEwen,et al.  Stress down-regulates corticosterone receptors in a site-specific manner in the brain. , 1984, Endocrinology.

[60]  S. Reppert,et al.  Maternal endocrine extirpations do not abolish maternal coordination of the fetal circadian clock. , 1986, Endocrinology.

[61]  E. van Cauter,et al.  Depression: A Disorder of Timekeeping? , 2015, Perspectives in biology and medicine.

[62]  N. Kalin,et al.  Prenatal stress alters brain catecholaminergic activity and potentiates stress-induced behavior in adult rats , 1992, Brain Research.

[63]  A. Kalsbeek,et al.  Novel environment induced inhibition of corticosterone secretion: physiological evidence for a suprachiasmatic nucleus mediated neuronal hypothalamo-adrenal cortex pathway , 1997, Brain Research.

[64]  U. Westphal,et al.  Influence of anterior pituitary hormones on the corticosteroid-binding globulin in the rat. , 1966, Endocrinology.

[65]  F. Holsboer,et al.  Plasticity of hippocampal corticosteroid receptors during aging in the rat , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[66]  G. Becker,et al.  Crucial role of the postnatal maternal environment in the expression of prenatal stress effects in the male rats. , 1977, Journal of comparative and physiological psychology.

[67]  B. Richardson,et al.  Effects of synthetic glucocorticoid administration on human fetal breathing movements at 34 to 35 weeks' gestational age. , 1981, American journal of obstetrics and gynecology.

[68]  J. Reul,et al.  Differential response of type I and type II corticosteroid receptors to changes in plasma steroid level and circadian rhythmicity. , 1987, Neuroendocrinology.

[69]  J. Joffe.  Genotype and Prenatal and Premating Stress Interact To Affect Adult Behavior in Rats , 1965, Science.

[70]  J. Stern,et al.  Failure of severe maternal stress or ACTH during pregnancy to affect emotionality of male rat offspring: implications of litter effects for prenatal studies. , 1979, Developmental psychobiology.

[71]  Molly Carnes,et al.  Pulsatile adrenocorticotropic hormone: An overview , 1997, Biological Psychiatry.

[72]  N. Kalin,et al.  Stressor controllability during pregnancy influences pituitary-adrenal hormone concentrations and analgesic responsiveness in offspring , 1988, Physiology & Behavior.

[73]  R. Spencer,et al.  Evidence for mineralocorticoid receptor facilitation of glucocorticoid receptor-dependent regulation of hypothalamic-pituitary-adrenal axis activity. , 1998, Endocrinology.

[74]  L. Takahashi.  Prenatal stress: consequences of glucocorticoids on hippocampal development and function , 1998, International Journal of Developmental Neuroscience.

[75]  D. Pringuey,et al.  Antidepressant effects of the sleep/wake cycle phase advance. Preliminary report. , 1987, Journal of affective disorders.

[76]  N. Mrosovsky,et al.  Phase angle changes of photically entrained circadian rhythms following a single nonphotic stimulus , 1994, Physiology & Behavior.

[77]  R. Bauman,et al.  Circadian effects of escapable and inescapable shock on the food intake and wheelrunning of rats , 1992, Physiology & Behavior.

[78]  M. Le Moal,et al.  Prenatal Stress Induces High Anxiety and Postnatal Handling Induces Low Anxiety in Adult Offspring: Correlation with Stress-Induced Corticosterone Secretion , 1997, The Journal of Neuroscience.

[79]  T. Deguchi.  Ontogenesis of a biological clock for serotonin:acetyl coenzyme A N-acetyltransferase in pineal gland of rat. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[80]  M. Le Moal,et al.  Adoption reverses the long-term impairment in glucocorticoid feedback induced by prenatal stress , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[81]  E. D. de Kloet,et al.  Relative occupation of type-I and type-II corticosteroid receptors in rat brain following stress and dexamethasone treatment: functional implications. , 1987, The Journal of endocrinology.

[82]  J. Schlechte,et al.  THE EFFECT OF GLUCOCORTICOIDS ON CORTICOSTEROID BINDING GLOBULIN , 1987, Clinical endocrinology.

[83]  P. Hartmann,et al.  Relationship between foetal corticosteroids, maternal progesterone and parturition in the rat. , 1977, Acta endocrinologica.

[84]  M. Weinstock.  Does Prenatal Stress Impair Coping and Regulation of Hypothalamic-Pituitary-Adrenal Axis? , 1997, Neuroscience & Biobehavioral Reviews.

[85]  G. Scatchard,et al.  THE ATTRACTIONS OF PROTEINS FOR SMALL MOLECULES AND IONS , 1949 .

[86]  W. Engeland,et al.  Splanchnic neural activity modulates ultradian and circadian rhythms in adrenocortical secretion in awake rats. , 1994, Neuroendocrinology.

[87]  M. Jouvet,et al.  Sleep increase after immobilization stress: role of the noradrenergic locus coeruleus system in the rat , 1995, Neuroscience Letters.

[88]  S. Shibata,et al.  Development of a fetal circadian rhythm after disruption of the maternal circadian system. , 1988, Brain research.

[89]  R. Morris,et al.  Glucocorticoids, hippocampal corticosteroid receptor gene expression and antidepressant treatment: relationship with spatial learning in young and aged rats , 1995, Neuroscience.

[90]  M. Dallman,et al.  Adrenal sensitivity to adrenocorticotropin varies diurnally. , 1981, Endocrinology.

[91]  K. Honma,et al.  Prenatal onset and maternal modifications of the circadian rhythm of plasma corticosterone in blind infantile rats. , 1982, The Journal of physiology.

[92]  D M Sheehan,et al.  Prenatal dexamethasone or stress but not ACTH or corticosterone alter sexual behavior in male rats. , 1995, Neurotoxicology and teratology.

[93]  E. Werstiuk,et al.  Dysregulation of neuroendocrine crossroads: Depression, orcadian rhythms and the retina — A hypothesis , 1987, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[94]  M. Le Moal,et al.  Prenatal Stress Enhances Stress- and Corticotropin-Releasing Factor-Induced Stimulation of Hippocampal Acetylcholine Release in Adult Rats , 1998, The Journal of Neuroscience.

[95]  F. Turek,et al.  Phase-shifting effects of acute increases in activity on circadian locomotor rhythms in hamsters. , 1991, The American journal of physiology.

[96]  P. Linkowski,et al.  The 24-hour profile of adrenocorticotropin and cortisol in major depressive illness. , 1985, The Journal of clinical endocrinology and metabolism.

[97]  Shakti Sharma,et al.  Sex-specific effects of prenatal stress on hypothalamic-pituitary-adrenal responses to stress and brain glucocorticoid receptor density in adult rats. , 1995, Brain research. Developmental brain research.

[98]  R. Porsolt,et al.  Depression: a new animal model sensitive to antidepressant treatments , 1977, Nature.

[99]  J. V. Van eekelen,et al.  Stress, glucocorticoids and development. , 1988, Progress in brain research.

[100]  J. Weisz,et al.  Differential effects of maternal stress on circulating levels of corticosterone, progesterone, and testosterone in male and female rat fetuses and their mothers. , 1984, Endocrinology.