Corticotropin-releasing Hormone Messenger Ribonucleic Acid Research Articles

Vulnerability to stress in mouse offspring is ameliorated when pregnant dams are provided a chewing stick during prenatal stress

ObjectiveTo investigate whether maternal chewing during prenatal stress alters the responsivity of young offspring to novel stress, we examined the expression of hippocampal glucocorticoid receptors and mineralocorticoid receptors, and the levels of hypothalamic corticotropin-releasing hormone in young adult mouse offspring of dams exposed to restraint stress during pregnancy. DesignTo induce stress, the dams were placed in a ventilated restraint tube for 45 min each day from day 12 of pregnancy through parturition. While restrained in the tube, one group of dams was provided a wooden stick for chewing. Hippocampal expression of glucocorticoid receptor and mineralocorticoid receptor messenger ribonucleic acid was assessed in 1-month-old pups. Hypothalamic expression of corticotropin-releasing hormone messenger ribonucleic acid was examined before and after exposing the offspring to a novel stressor. ResultsPrenatal stress significantly decreased hippocampal expression of both glucocorticoid receptor and mineralocorticoid receptor messenger ribonucleic acid in the offspring, and increased the expression of corticotropin-releasing hormone messenger ribonucleic acid in the hypothalamic paraventricular nucleus in the offspring after novel stress exposure. Maternal chewing during exposure to prenatal stress attenuated the decreased hippocampal expression of both glucocorticoid receptor and mineralocorticoid receptor messenger ribonucleic acid, and the increased corticotropin-releasing hormone messenger ribonucleic acid expression in the hypothalamic paraventricular nucleus in the offspring. ConclusionsDownregulation of hippocampal glucocorticoid receptor and mineralocorticoid receptor expression in offspring due to prenatal stress, which may be associated with increased susceptibility to novel stress in adulthood, are attenuated by allowing the dams to chew on a wooden stick.

Gender and puberty interact on the stress-induced activation of parvocellular neurosecretory neurons and corticotropin-releasing hormone messenger ribonucleic acid expression in the rat.

Individual variations in hypothalamic-pituitary-adrenal (HPA) function are most evident at or beyond the time of puberty, when marked changes in sex steroid release occur. To explore the nature by which gender differences in HPA function emerge we examined in prepubertal (approximately 30-d-old) and postpubertal (approximately 60-d-old) male and female rats HPA activity under basal conditions and in response to 30 min of restraint. Within the ACTH-regulating, medial parvocellular portion of the paraventricular nucleus, restraint-induced Fos protein and arginine vasopressin heteronuclear RNA were lower in 60- than in 30-d-old males. No such age-related shift in the response of these synaptic and transcriptional markers of cellular activation occurred in female rats. Basal CRH mRNA expression levels in the paraventricular nucleus increased with age in female but not male rats. Conversely, only male rats showed an age-related increase in basal CRH mRNA in the central amygdala, suggesting that neuronal and neurosecretory CRH-expressing cell types are subject to different pubertal and gender influences. We conclude that gonadal regulation of the HPA axis develops via distinct mechanisms in males and females. Puberty-related shifts in parvocellular neurosecretory function in males are emphasized by stress-induced shifts in neuronal activation, whereas biosynthetic alterations dominate in female rats.

Expression of Corticotropin-Releasing Hormone Messenger Ribonucleic Acid in Human Pituitary Corticotroph Adenomas Associated with Proliferative Potential

Expression of Corticotropin-Releasing Hormone Messenger Ribonucleic Acid in Human Pituitary Corticotroph Adenomas Associated with Proliferative Potential

Expression of corticotropin-releasing hormone messenger ribonucleic acid in human pituitary corticotroph adenomas associated with proliferative potential.

Among the factors that promote the growth of human pituitary corticotroph adenomas (hPCAs), the proliferative potential of CRH secreted by hPCAs on these tumors is not well known. In this study, the CRH messenger ribonucleic acid (mRNA) transcripts were demonstrated on paraffin sections using the quantitative in situ hybridization method in 37 of 43 hPCAs, including 17 of 22 microadenomas, 15 of 15 macroadenomas, and 5 of 6 locally invasive adenomas according to Hardy's classification of pituitary adenomas. The more important findings were that CRH mRNA signal intensity in pituitary corticotroph adenoma cells was linearly correlated with Ki-67 tumor growth fractions (r = 0.802; P < 0.0001), and in macroadenoma and locally invasive adenoma cells it was significantly higher than in microadenoma cells (P = 0.035). On the other hand, CRH mRNA transcript accumulation was absent or negligible in 10 normal pituitary glands (P = 0.005). This is the first report of the frequent expression of CRH mRNA localized in human pituitary corticotroph adenoma cells. These results indicate that CRH from a local source of corticotroph adenoma cells not only has autocrine/paracrine functions in corticotroph adenomatous tissue, but also is an important factor associated with a proliferative potential of hPCAs.

Emergence of an Isolated Arginine Vasopressin (AVP) Response to Stress after Repeated Restraint: A Study of Both AVP and Corticotropin-Releasing Hormone Messenger Ribonucleic Acid (RNA) and Heteronuclear RNA

Emergence of an Isolated Arginine Vasopressin (AVP) Response to Stress after Repeated Restraint: A Study of Both AVP and Corticotropin-Releasing Hormone Messenger Ribonucleic Acid (RNA) and Heteronuclear RNA

Emergence of an isolated arginine vasopressin (AVP) response to stress after repeated restraint: a study of both AVP and corticotropin-releasing hormone messenger ribonucleic acid (RNA) and heteronuclear RNA.

The hypothalamic-pituitary-adrenal axis adapts to periods of chronic or repeated stress. We have now investigated whether there is any differential effect of repeated immobilization stress on CRH and arginine vasopressin (AVP) gene transcription in the hypothalamic paraventricular nucleus (PVN), using probes for both intronic and exonic sequences of the AVP and CRH genes. Daily restraint for 13 days had no significant affect on basal corticosterone level, CRH heteronuclear RNA (hnRNA), CRH messenger RNA (mRNA), AVP hnRNA, or AVP mRNA. After the final episode of acute restraint, on day 14, there was a rapid increase in plasma corticosterone and AVP hnRNA level in the parvocellular subdivision of the PVN, a slower increase in AVP mRNA level in the parvocellular subdivision of the PVN, but no significant change in either CRH hnRNA or CRH mRNA in the PVN. The increase in AVP hnRNA and mRNA was specific to the parvocellular PVN, because there was no change in either transcript in the magnocellular cells of this nucleus. This isolated response is in marked contrast to naive rats, which show a predominant CRH hnRNA and mRNA response, and infers that part of the adaptation to repeated stress results from a down-regulation of CRH gene responsiveness with maintenance or even a compensatory increase in the AVP gene response.

Thyroid hormone-mediated regulation of corticotropin-releasing hormone messenger ribonucleic acid in the rat.

We have used in situ hybridization histochemistry to investigate interactions between the thyroid and adrenal axes in the rat. Propylthiouracil (PTU)-induced hypothyroidism caused a significant reduction in CRH gene transcripts in the paraventricular nucleus of male rats, with a concomitant decrease in both POMC gene expression in the anterior pituitary gland and circulating corticosterone. Conversely, adrenalectomy alone or adrenalectomy with high dose corticosterone pellet replacement had no significant effect on the thyroid hormone axis. The effect of thyroid hormones on the adrenal axis was not secondary to changes in the level of circulating corticosteroids, as the same effect of PTU-induced hypothyroidism was seen in adrenalectomized rats given corticosterone replacement. Neither was the effect of PTU simply the result of a direct toxic effect on the hypothalamus, as concurrent treatment with T3 blocked the response. We conclude that circulating levels of thyroid hormones have a major effect on the central regulation of the hypothalamic-pituitary-adrenal axis.

Thyroid hormone-mediated regulation of corticotropin-releasing hormone messenger ribonucleic acid in the rat

Thyroid hormone-mediated regulation of corticotropin-releasing hormone messenger ribonucleic acid in the rat

Levels of corticotropin-releasing hormone messenger ribonucleic acid (mRNA) in the hypothalamic paraventricular nucleus and proopiomelanocortin mRNA in the anterior pituitary during late gestation in fetal sheep

Levels of corticotropin-releasing hormone messenger ribonucleic acid (mRNA) in the hypothalamic paraventricular nucleus and proopiomelanocortin mRNA in the anterior pituitary during late gestation in fetal sheep

Levels of corticotropin-releasing hormone messenger ribonucleic acid (mRNA) in the hypothalamic paraventricular nucleus and proopiomelanocortin mRNA in the anterior pituitary during late gestation in fetal sheep.

CRH regulates POMC gene expression and subsequent ACTH biosynthesis and release. In sheep, the preterm rise in fetal plasma ACTH commences at approximately 125 days gestation (dGA; 147 dGA = term), preceding the initiation of adrenocortical steroidogenesis. We hypothesized that an increase in CRH expression in the hypothalamic paraventricular nucleus (PVN) and POMC expression in the anterior pituitary in the late gestation sheep fetus may precede adrenal cortex maturation. Fetal sheep were obtained at 105-107 (n = 4), 128-130 (n = 5), and 138-140 (n = 4) dGA. Hypothalami were cryosectioned and subjected to in situ hybridization for ovine CRH mRNA. In all dGA groups, expression of CRH mRNA was observed throughout the rostrocaudal extent of the fetal PVN. The midrostral region of the fetal PVN where the dorsal and ventral divisions of the rostral PVN merge to form a single structure was selected for quantification. The number of copies of CRH probe hybridized per micron 3 were determined to estimate the quantity of hybridized CRH mRNA; the mean estimated CRH mRNA copy number per micron 3 midrostral PVN were 0.064 +/- 0.012 (105-107 dGA), 0.237 +/- 0.048 (128-130 dGA), and 0.108 +/- 0.034 (138-140 dGA; mean +/- SEM copies per micron 3 PVN). CRH mRNA signal significantly increased between 105-107 and 128-130 dGA (P < or = 0.05); 138-140 dGA levels of mRNA were not different from either 105-107 or 128-140 dGA levels. Regional variation in CRH mRNA levels were observed within the midrostral PVN between groups; at 138-140 dGA, a population of lateral midrostral PVN neurons maintain CRH mRNA levels greater than 105-107 dGA (P < 0.05), similar to those at 128-130 dGA. Fetal anterior pituitary RNA was subjected to Northern analysis for POMC mRNA. POMC mRNA levels in fetal anterior pituitaries were 14.1 +/- 2.2 (105-107 dGA), 28.9 +/- 10.9 (128-130 dGA), and 43.2 +/- 6 (138-140 dGA; mean +/- SEM arbitrary units). A significant increase (P < or = 0.05) was observed at 138-140 dGA compared to levels at 105-107 dGA. We conclude CRH mRNA levels in the fetal PVN increase coincident with increased POMC gene expression and the late gestation rise in fetal plasma ACTH. We speculate that a neuroendocrine stimulus at the fetal PVN may precipitate increased levels of CRH mRNA, initiating the maturation of the fetal hypothalamic-hypophyseal-adrenal axis, thus inducing the events of labor and delivery in sheep.

Hypotensive hemorrhage elevates corticotropin-releasing hormone messenger ribonucleic acid (mRNA) but not vasopressin mRNA in the rat hypothalamus.

We examined the effect of acute hypotensive hemorrhage on corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) messenger RNAs (mRNAs) in neurons of the rat hypothalamus. Sprague-Dawley male rats were cannulated (femoral artery and vein) and received a 15 ml/kg.3 min hemorrhage on the morning of the fourth day. Time controls received no hemorrhage. After light halothane anesthesia, the rats were decapitated at 1 or 4 h (six to nine rats per group). The hypothalami were removed, frozen, and sectioned at 12 microns. In situ hybridization was performed using two 48-base oligodeoxynucleotide probes for CRH and AVP message, respectively. Hemorrhage led to a fall in arterial blood pressure and heart rate that recovered by 1 h. Plasma ACTH, corticosterone, and AVP were elevated 20, 60, and 90 min after hemorrhage, but returned to near control levels by 4 h. CRH mRNA was significantly elevated 1 and 4 h after hemorrhage, as compared to time controls, in parvocellular neurons of the paraventricular nuclei. However, AVP mRNA was not different from controls at 1 or 4 h after hemorrhage in the magnocellular or parvocellular paraventricular nuclei, or in the supraoptic or accessory nuclei of the hypothalamus. AVP mRNA was also found in neurons of the suprachiasmatic nuclei, but there was no difference in the amount of mRNA between the 1-h hemorrhage and control groups. These data suggest that neural signals, originating for cardiovascular receptors activated by hemorrhage, up-regulate message for CRH but not for AVP in the paraventricular nuclei of the rat hypothalamus.

Hypotensive hemorrhage elevates corticotropin-releasing hormone messenger ribonucleic acid (mRNA) but not vasopressin mRNA in the rat hypothalamus

Hypotensive hemorrhage elevates corticotropin-releasing hormone messenger ribonucleic acid (mRNA) but not vasopressin mRNA in the rat hypothalamus