Journal of Clinical Endocrinology & Metabolism, Vol 81, 763-769, Copyright © 1996 by Endocrine Society

ARTICLES

Nitric oxide regulation of corticotropin-releasing hormone release from the human perfused placenta in vitro

CM Roe, IM Leitch, AL Boura and R Smith
Maternal Health Research Center, John Hunter Hospital, Newcastle, New South Wales, Australia.

We have investigated the regulatory role of nitric oxide (NO) in corticotropin-releasing hormone (CRH) release from the human perfused placental lobule in vitro. The effects of the NO donor sodium nitroprusside, the NO synthase inhibitor N omega-nitro-L-arginine, and the NO substrate L-arginine on human (h) placental CRH secretion have been studied. Single lobules of term placentae were bilaterally perfused with Krebs solution (5 mL/min; 95% O2-5% CO2; 37 C; pH 7.3). Fetal and maternal perfusates were collected at 4 C every 30 min for 3 h. CRH immunoreactivity (CRH-IR) in perfusates was measured by RIA using the 41-residue synthetic CRH as standard, 125I-labeled Tyr-hCRH as tracer, and a rabbit anti-CRH antibody Y2BO. The sensitivity of the assay was 0.13 pmol/L. Under basal conditions, human perfused placentae in vitro continuously secreted CRH-IR, which diluted in parallel to a synthetic hCRH-(1-41) standard curve. Size-exclusion chromatography of placental perfusates using a Sephadex G-50 column indicated that placental CRH-IR predominately coeluted with hCRH-(1-41) standard. Basal maternal perfusate CRH-IR levels (27 +/- 4 pmol/L) released from perfused placental lobules were nearly 10-fold greater than fetal perfusate CRH-IR levels (3.4 +/- 0.7 pmol/L; P < 0.05). Infusion of sodium nitroprusside (30-100 mumol/L) into the maternal and fetal placental circulations inhibited CRH-IR release into maternal perfusate in a concentration-dependent manner, but did not inhibit CRH-IR release into the fetal perfusate. N omega-nitro-L-arginine (100 mumol/L) increased placental CRH-IR secretion into fetal perfusate, and this effect was reversed by the infusion of L-arginine (100 mumol/L), which also reduced release below basal levels. In contrast, maternal perfusate CRH-IR levels were not affected by N omega-nitro-L-arginine or L-arginine. These results indicate that the human perfused placenta in vitro releases a substance of similar mol wt and hCRH-IR. Moreover, modulators of the NO signaling pathway differentially affect placental secretion of CRH-IR into the maternal and fetal perfusates. These data are consistent with the involvement of NO in the regulation of placental CRH release during pregnancy.

This article has been cited by other articles:

				P. Florio, F. M. Severi, G. Fiore, L. Micheli, C. Bocchi, C. Nencini, I. Pezzani, G. Giorgi, and F. Petraglia Impaired Uterine Artery Blood Flow at Mid Gestation and Low Levels of Maternal Plasma Corticotropin-Releasing Factor Reproductive Sciences, July 1, 2003; 10(5): 294 - 297. [Abstract] [PDF]

				P. Navarra, F. Miceli, G. Tringali, F. Minici, M. G. Pardo, A. Lanzone, S. Mancuso, and R. Apa Evidence for a Functional Link between the Heme Oxygenase-Carbon Monoxide Pathway and Corticotropin-Releasing Hormone Release from Primary Cultures of Human Trophoblast Cells J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 317 - 323. [Abstract] [Full Text]

				K. Linnemann, A. Malek, R. Sager, W. F. Blum, H. Schneider, and C. Fusch Leptin Production and Release in the Dually in VitroPerfused Human Placenta J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4298 - 4301. [Abstract] [Full Text]

				A. Slominski, J. Wortsman, T. Luger, R. Paus, and S. Solomon Corticotropin Releasing Hormone and Proopiomelanocortin Involvement in the Cutaneous Response to Stress Physiol Rev, July 1, 2000; 80(3): 979 - 1020. [Abstract] [Full Text] [PDF]

				I. M. Leitch, A. L. A. Boura, C. Botti, M. A. Read, W. A. W. Walters, and R. Smith Vasodilator Actions of Urocortin and Related Peptides in the Human Perfused Placenta in Vitro J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4510 - 4513. [Abstract] [Full Text]

				T. C. Theoharides, L. K. Singh, W. Boucher, X. Pang, R. Letourneau, E. Webster, and G. Chrousos Corticotropin-Releasing Hormone Induces Skin Mast Cell Degranulation and Increased Vascular Permeability, A Possible Explanation for Its Proinflammatory Effects Endocrinology, January 1, 1998; 139(1): 403 - 413. [Abstract] [Full Text] [PDF]

				X. Ni, E.-C. Chan, J. T. Fitter, and R. Smith Nitric Oxide Inhibits Corticotropin-Releasing Hormone Exocytosis But Not Synthesis by Cultured Human Trophoblasts J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 4171 - 4175. [Abstract] [Full Text] [PDF]