This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chan, E.-C. Articles by Smith, R. Search for Related Content PubMed PubMed Citation Articles by Chan, E.-C. Articles by Smith, R. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Childbirth Hazardous Substances DB HYDROCORTISONE PYRROLE

A Corticotropin-Releasing Hormone Type I Receptor Antagonist Delays Parturition in Sheep

Maternal Health Research Centre (E.C.C., J.F., G.M., R.S.), John Hunter Hospital, Locked Bag 1, HRMC, NSW 2310, Australia; Develpmental Endocrinology Branch (E.W., G.P.C.), NICHD, and Medicinal Chemistry Branch (K.R.), NIDDK, NIH, Bethesda, Maryland 20817-6154

Address all correspondence and requests for reprints to: Roger Smith, John Hunter Hospital, Maternal Health Research Centre, Locked Bag 1, HRMC, Newcastle 2310, Australia.

	Abstract

Top Abstract

 
In sheep, corticotropin-releasing homone (CRH) can stimulate the fetal release of ACTH to produce a cortisol surge which leads to the onset of parturition. We tested the hypothesis that fetal CRH is a primary factor in the onset of parturition in sheep by using a Type I CRH receptor antagonist, antalarmin, to block the endogenous action of CRH. Pregnant ewes were cannulated at 130—135 days of gestation. Five catheters were placed into the amniotic sac, fetal femoral artery, fetal tarsal vein, maternal jugular vein and carotid artery. After 5 days’ recovery, blood samples from maternal and fetal vessels were collected at the following times: a day before the start of infusion, at {-1, 0, 1, 2, 4, 8 and 24} h, on the first day of infusion, and thereafter daily throughout a 10-day infusion. Animals (n=6 per group) received infusions into a fetal vein of either a vehicle comprising 1:1 mixture of ethanol and polyethoxylated castor oil (Cremophor EL) or antalarmin (50 g/L) in the vehicle at a rate of 0.3 mL/h. The plasma samples were assayed for ACTH and cortisol using commercial RIA kits. Fetuses infused with vehicle delivered at a mean gestational age of 141.8 ± 0.9 days compared with antalarmin-infused sheep at 148.8 ± 1.6 days (P = 0.0036, unpaired Student’s t-test). Fetal ACTH and cortisol did not change in the antalarmin-infused sheep after 3 days’ infusion compared to significant increases in vehicle-infused sheep )P=0.004 and P = 0.016 respectively, ANOVA). These data show that CRH receptor antagonism in the fetus can delay the onset of parturition. It supports the hypothesis that hypothalamic CRH drives fetal production of ACTH and is essential for the onset of parturition triggered by a surge in fetal cortisol.

Received March 4, 1998.

This article has been cited by other articles:

				J. W. Rich-Edwards, A. P. Mohllajee, K. Kleinman, M. R. Hacker, J. Majzoub, R. J. Wright, and M. W. Gillman Elevated Midpregnancy Corticotropin-Releasing Hormone Is Associated with Prenatal, But Not Postpartum, Maternal Depression J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1946 - 1951. [Abstract] [Full Text] [PDF]

				G. Mastorakos, E. I Karoutsou, and M. Mizamtsidi Corticotropin releasing hormone and the immune/inflammatory response Eur. J. Endocrinol., November 1, 2006; 155(suppl_1): S77 - S84. [Abstract] [Full Text] [PDF]

				E Zoumakis, D K Grammatopoulos, and G P Chrousos Corticotropin-releasing hormone receptor antagonists Eur. J. Endocrinol., November 1, 2006; 155(suppl_1): S85 - S91. [Abstract] [Full Text] [PDF]

				R. Sirianni, B. A. Mayhew, B. R. Carr, C. R. Parker Jr., and W. E. Rainey Corticotropin-Releasing Hormone (CRH) and Urocortin Act through Type 1 CRH Receptors to Stimulate Dehydroepiandrosterone Sulfate Production in Human Fetal Adrenal Cells J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5393 - 5400. [Abstract] [Full Text] [PDF]

				D. A. Myers, P. A. Bell, K. Hyatt, M. Mlynarczyk, and C. A. Ducsay Long-term hypoxia enhances proopiomelanocortin processing in the near-term ovine fetus Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2005; 288(5): R1178 - R1184. [Abstract] [Full Text] [PDF]

				A. C. Holloway, D. C. Howe, G. Chan, V. L. Clifton, R. Smith, and J. R. G. Challis Urocortin: a mechanism for the sustained activation of the HPA axis in the late-gestation ovine fetus? Am J Physiol Endocrinol Metab, July 1, 2002; 283(1): E165 - E171. [Abstract] [Full Text] [PDF]

				K. Erickson, P. Thorsen, G. Chrousos, D. E. Grigoriadis, O. Khongsaly, J. McGregor, and J. Schulkin Preterm Birth: Associated Neuroendocrine, Medical, and Behavioral Risk Factors J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2544 - 2552. [Abstract] [Full Text] [PDF]

				T.M. O'CONNOR, D.J. O'HALLORAN, and F. SHANAHAN The stress response and the hypothalamic-pituitary-adrenal axis: from molecule to melancholia QJM, June 1, 2000; 93(6): 323 - 333. [Abstract] [Full Text] [PDF]

				D. A. Myers, M. E. Bell, T. J. McDonald, and T. R. Myers Corticotropin-Releasing Factor Receptor Expression in the Pituitary of Fetal Sheep after Lesion of the Hypothalamic Paraventricular Nucleus Endocrinology, September 1, 1999; 140(9): 4292 - 4299. [Abstract] [Full Text]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chan, E.-C. Articles by Smith, R. Search for Related Content PubMed PubMed Citation Articles by Chan, E.-C. Articles by Smith, R. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Childbirth Hazardous Substances DB HYDROCORTISONE PYRROLE