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Effects of fetal ethanol exposure on pituitary-adrenal sensitivity to secretagogues.
Alcohol Clin Exp Res. 2000 Jul; 24(7):1110-9.AC

Abstract

BACKGROUND

Rodents prenatally exposed to ethanol demonstrate hormonal hyper-responsiveness to stressors in adulthood. The present study examined the hypothesis that an increased sensitivity of the adrenal to ACTH and/or the pituitary to corticotropin releasing hormone (CRH) after dexamethasone suppression, may play a role in the hormonal hyper-responsiveness seen in fetal ethanol-exposed rats.

METHODS

Sprague-Dawley males and females from prenatal ethanol-exposed (E), pair-fed (PF), and ad libitum-fed control (C) groups were tested in adulthood (90-120 days). Testing was done in a series of two experiments carried out during the trough of the corticosterone rhythm, the time of greatest sensitivity to feedback inhibition. Twenty-four to 48 hr before testing, jugular cannulae were implanted for hormone infusion and blood sample collection. In both experiments, animals were injected intraperitoneally with dexamethasone-21-phosphate (DEX) (15 microg/100 g body weight for males or 30 microg/100 g body weight for females) 3 hr before testing to suppress endogenous hypothalamic-pituitary-adrenal (HPA) activity. Animals were given a bolus infusion of ACTH (0-0.10 mg/rat) and blood samples (0.2 cc) were drawn at 60-min intervals over 240 min for determination of plasma corticosterone (CORT) levels (Experiment 1), or were given a bolus infusion of CRH (0-20 microg/kg body wt) and samples drawn at 0, 5, 15, and 30 min for determination of plasma ACTH and CORT levels (Experiment 2).

RESULTS

As expected, sex differences in adrenal response to ACTH and pituitary response to CRH were observed; females had higher CORT and ACTH levels than males at all concentrations of ACTH and CRH. In addition, dose-response relationships between exogenously administered ACTH or CRH and plasma CORT were demonstrated; increasing concentrations of secretagogues resulted in higher and/or more prolonged CORT responses in both males and females. There were no significant differences among E, PF, and C males or females in adrenal sensitivity to ACTH. However, prenatal ethanol exposure altered pituitary sensitivity to CRH in both males and females. E and PF males demonstrated increased plasma ACTH but not CORT compared with C males, whereas E females demonstrated increased plasma ACTH and CORT levels compared with PF and C females after CRH infusion.

CONCLUSIONS

Together these data suggest that (1) E animals do not show increased adrenal sensitivity to ACTH compared with controls; (2) the insult of prenatal ethanol exposure may result in altered pituitary sensitivity to CRH after DEX suppression; and (3) there may be a sex-specific difference in sensitivity of the mechanism(s) underlying HPA hyper-responsiveness.

Authors+Show Affiliations

Department of Anatomy, Faculty of Medicine, University of British Columbia, Vancouver, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10924017

Citation

Osborn, J A., et al. "Effects of Fetal Ethanol Exposure On Pituitary-adrenal Sensitivity to Secretagogues." Alcoholism, Clinical and Experimental Research, vol. 24, no. 7, 2000, pp. 1110-9.
Osborn JA, Yu C, Stelzl GE, et al. Effects of fetal ethanol exposure on pituitary-adrenal sensitivity to secretagogues. Alcohol Clin Exp Res. 2000;24(7):1110-9.
Osborn, J. A., Yu, C., Stelzl, G. E., & Weinberg, J. (2000). Effects of fetal ethanol exposure on pituitary-adrenal sensitivity to secretagogues. Alcoholism, Clinical and Experimental Research, 24(7), 1110-9.
Osborn JA, et al. Effects of Fetal Ethanol Exposure On Pituitary-adrenal Sensitivity to Secretagogues. Alcohol Clin Exp Res. 2000;24(7):1110-9. PubMed PMID: 10924017.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of fetal ethanol exposure on pituitary-adrenal sensitivity to secretagogues. AU - Osborn,J A, AU - Yu,C, AU - Stelzl,G E, AU - Weinberg,J, PY - 2000/8/3/pubmed PY - 2001/2/28/medline PY - 2000/8/3/entrez SP - 1110 EP - 9 JF - Alcoholism, clinical and experimental research JO - Alcohol. Clin. Exp. Res. VL - 24 IS - 7 N2 - BACKGROUND: Rodents prenatally exposed to ethanol demonstrate hormonal hyper-responsiveness to stressors in adulthood. The present study examined the hypothesis that an increased sensitivity of the adrenal to ACTH and/or the pituitary to corticotropin releasing hormone (CRH) after dexamethasone suppression, may play a role in the hormonal hyper-responsiveness seen in fetal ethanol-exposed rats. METHODS: Sprague-Dawley males and females from prenatal ethanol-exposed (E), pair-fed (PF), and ad libitum-fed control (C) groups were tested in adulthood (90-120 days). Testing was done in a series of two experiments carried out during the trough of the corticosterone rhythm, the time of greatest sensitivity to feedback inhibition. Twenty-four to 48 hr before testing, jugular cannulae were implanted for hormone infusion and blood sample collection. In both experiments, animals were injected intraperitoneally with dexamethasone-21-phosphate (DEX) (15 microg/100 g body weight for males or 30 microg/100 g body weight for females) 3 hr before testing to suppress endogenous hypothalamic-pituitary-adrenal (HPA) activity. Animals were given a bolus infusion of ACTH (0-0.10 mg/rat) and blood samples (0.2 cc) were drawn at 60-min intervals over 240 min for determination of plasma corticosterone (CORT) levels (Experiment 1), or were given a bolus infusion of CRH (0-20 microg/kg body wt) and samples drawn at 0, 5, 15, and 30 min for determination of plasma ACTH and CORT levels (Experiment 2). RESULTS: As expected, sex differences in adrenal response to ACTH and pituitary response to CRH were observed; females had higher CORT and ACTH levels than males at all concentrations of ACTH and CRH. In addition, dose-response relationships between exogenously administered ACTH or CRH and plasma CORT were demonstrated; increasing concentrations of secretagogues resulted in higher and/or more prolonged CORT responses in both males and females. There were no significant differences among E, PF, and C males or females in adrenal sensitivity to ACTH. However, prenatal ethanol exposure altered pituitary sensitivity to CRH in both males and females. E and PF males demonstrated increased plasma ACTH but not CORT compared with C males, whereas E females demonstrated increased plasma ACTH and CORT levels compared with PF and C females after CRH infusion. CONCLUSIONS: Together these data suggest that (1) E animals do not show increased adrenal sensitivity to ACTH compared with controls; (2) the insult of prenatal ethanol exposure may result in altered pituitary sensitivity to CRH after DEX suppression; and (3) there may be a sex-specific difference in sensitivity of the mechanism(s) underlying HPA hyper-responsiveness. SN - 0145-6008 UR - https://www.unboundmedicine.com/medline/citation/10924017/Effects_of_fetal_ethanol_exposure_on_pituitary_adrenal_sensitivity_to_secretagogues_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0145-6008&date=2000&volume=24&issue=7&spage=1110 DB - PRIME DP - Unbound Medicine ER -