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Titolo:
ENDOCRINE PROFILE AND NEUROENDOCRINE CHALLENGE TESTS IN TRANSGENIC MICE EXPRESSING ANTISENSE RNA AGAINST THE GLUCOCORTICOID RECEPTOR
Autore:
BARDEN N; STEC ISM; MONTKOWSKI A; HOLSBOER F; REUL JMHM;
Indirizzi:
MAX PLANCK INST PSYCHIAT,INST CLIN,KRAEPELINSTR 2 D-80804 MUNICH GERMANY MAX PLANCK INST PSYCHIAT,INST CLIN D-80804 MUNICH GERMANY UNIV LAVAL,DEPT PHYSIOL ST FOY PQ G1K 7P4 CANADA CHUL,RES CTR ST FOY PQ CANADA
Titolo Testata:
Neuroendocrinology
fascicolo: 3, volume: 66, anno: 1997,
pagine: 212 - 220
SICI:
0028-3835(1997)66:3<212:EPANCT>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
CORTICOTROPIN-RELEASING FACTOR; CENTRAL-NERVOUS-SYSTEM; ADRENOCORTICOTROPIN SECRETION; ACTH-SECRETION; RAT-BRAIN; CORTICOSTEROID RECEPTORS; DOPAMINE RESPONSIVENESS; MESSENGER-RNAS; DEPRESSION; HORMONE;
Keywords:
ADRENAL STEROID RECEPTORS; CORTICOTROPIN; PROOPIOMELANOCORTIN; CORTICOTROPIN-RELEASING HORMONE; TRANSGENIC MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
45
Recensione:
Indirizzi per estratti:
Citazione:
N. Barden et al., "ENDOCRINE PROFILE AND NEUROENDOCRINE CHALLENGE TESTS IN TRANSGENIC MICE EXPRESSING ANTISENSE RNA AGAINST THE GLUCOCORTICOID RECEPTOR", Neuroendocrinology, 66(3), 1997, pp. 212-220

Abstract

A transgene expressing antisense RNA complementary to a fragment of the glucocorticoid receptor cDNA was incorporated into the mouse genomeand resulted in a transgenic animal that has decreased glucocorticoidreceptor function, The transgenic mice showed basal plasma ACTH and corticosterone levels similar to those of the normal control animals, We have further investigated changes in HPA axis regulation by use of different neuroendocrine challenge tests including a dexamethasone suppression test (DST), In comparison to normal mice, a tenfold higher dose of dexamethasone (i.e. 20 mu g/100 g body weight) was required to suppress the basal corticosterone levels of transgenic mice. Dexamethasone (2 mu g/100 g body weight) produced a long-lasting suppression of plasma ACTH and corticosterone levels in control mice, whereas in transgenic animals only a short-lasting decrease in ACTH levels was apparent. Corticotropin-releasing hormone (CRH) administration resulted in anenhanced response in plasma BCTH levels in transgenic mice, whereas the corticosterone response was markedly reduced. The discrepancy between ACTH and corresponding corticosterone secretions in transgenic micecould be attributed, in part, to a reduced sensitivity of the adrenalgland to stimulation by ACTH, Pituitaries of transgenic mice contained about 50% less proopiomelanocortin (POMC) mRNA than those of controlanimals. No significant differences were noted in the ACTH or proteincontents of normal and transgenic mice pituitary glands although a slight increase in protein content of the transgenic mouse adrenal glandwas apparent, In conclusion, transgenic mice with impaired GR function show major disturbances in HPA axis regulation which seem to be caused by the primary defect in conjunction with secondary modifications in, amongst others, pituitary CRH receptor system(s), sympathetic output and adrenal development, This mouse is therefore a useful model to study the consequences of life-long defective CR function and HPA axis regulation in general.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 12:56:24