Regulation of corticotropin-releasing hormone receptor messenger ribonucleic acid in the rat brain and pituitary by glucocorticoids and stress. 1995

S Makino, and J Schulkin, and M A Smith, and K Pacák, and M Palkovits, and P W Gold
Clinical Neuroendocrinology Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA.

Glucocorticoids and stress are known to influence the synthesis of corticotropin-releasing hormone (CRH) at a variety of sites in brain, including the hypothalamus and amygdala. The recent cloning of the CRH receptor (CRH-R) enabled us to determine whether glucocorticoids or stress influenced CRH action via regulation of CRH-R. We, therefore, used in situ hybridization to measure CRH-R messenger RNA (mRNA) levels in the hypothalamic paraventricular nucleus (PVN), anterior pituitary (AP), amygdala, and bed nucleus of the stria terminalis (BNST) under several conditions. Systemic corticosterone (CORT) treatment, both daily injection (5 mg/rat.day) up to 14 days and pellet implant (200 mg) for 14 days, decreased CRH-R mRNA in the PVN and lateral and basolateral nucleus of the amygdala (BLA). Corticosterone injection (10 mg/rat.day, for 7 days) decreased CRH-R mRNA in the AP. Adrenalectomy also decreased CRH-R mRNA in the PVN and AP, but did not alter it in the BLA. In both sham and adrenalectomized rats with CORT pellet replacement (39 mg; ADX+CORT rats), acute (2-h) and repeated (2 h daily for 14 days) immobilization stress (which produced a large increase in plasma CORT in sham rats) increased CRH-R mRNA in the PVN and decreased it in the AP, but did not affect CRH-R mRNA in the BLA. However, ADX+CORT rats consistently had higher levels of CRH-R mRNA in both the PVN and AP than sham rats after stress. Brain stem hemisection, which damaged all ascending catecholaminergic fibers with the exception of the locus ceruleus, attenuated immobilization stress-induced up-regulation of CRH-R mRNA ipsilaterally in the PVN. None of the treatments affected CRH-R mRNA levels in the central and medial nucleus of the amygdala or the BNST. These results suggest that high concentrations of CORT or CRH synergistically decrease CRH-R mRNA levels in the AP, and that at least high CORT has an inhibitory effect on PVN CRH-R mRNA levels. However, stress input can override such inhibitory effects and thus up-regulate CRH-R mRNA in the PVN. The extrahypothalamic regions, such as amygdala and BNST may have different sensitivities to CORT or CRH for the regulation of CRH-R mRNA.

UI MeSH Term Description Entries
D008297 Male Males
D010286 Paraventricular Hypothalamic Nucleus Nucleus in the anterior part of the HYPOTHALAMUS. Hypothalamic Paraventricular Nucleus,Paraventricular Nucleus,Hypothalamic Nucleus, Paraventricular,Nucleus, Hypothalamic Paraventricular,Nucleus, Paraventricular,Nucleus, Paraventricular Hypothalamic,Paraventricular Nucleus, Hypothalamic
D010903 Pituitary Gland, Anterior The anterior glandular lobe of the pituitary gland, also known as the adenohypophysis. It secretes the ADENOHYPOPHYSEAL HORMONES that regulate vital functions such as GROWTH; METABOLISM; and REPRODUCTION. Adenohypophysis,Anterior Lobe of Pituitary,Anterior Pituitary Gland,Lobus Anterior,Pars Distalis of Pituitary,Adenohypophyses,Anterior Pituitary Glands,Anterior, Lobus,Anteriors, Lobus,Lobus Anteriors,Pituitary Anterior Lobe,Pituitary Glands, Anterior,Pituitary Pars Distalis
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
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)
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D005938 Glucocorticoids A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. Glucocorticoid,Glucocorticoid Effect,Glucorticoid Effects,Effect, Glucocorticoid,Effects, Glucorticoid
D000324 Adrenocorticotropic Hormone An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP). ACTH,Adrenocorticotropin,Corticotropin,1-39 ACTH,ACTH (1-39),Adrenocorticotrophic Hormone,Corticotrophin,Corticotrophin (1-39),Corticotropin (1-39),Hormone, Adrenocorticotrophic,Hormone, Adrenocorticotropic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated

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