Journal of Clinical Endocrinology & Metabolism, Vol 79, 519-524, Copyright © 1994 by Endocrine Society

ARTICLES

Basal and KCl-stimulated corticotropin-releasing hormone release from human placental syncytiotrophoblasts is inhibited by sodium nitroprusside

K Sun, R Smith and PJ Robinson
Maternal Health Research Center, John Hunter Hospital, Newcastle, New South Wales, Australia.

Human placenta synthesizes and secretes large amounts of CRH during the second and third trimesters. In the hypothalamus, nitric oxide (NO) has been reported to affect CRH release. We studied the effect of NO on the regulation of placental CRH secretion. The effect of the NO donor sodium nitroprusside (SNP) on basal and KCl-stimulated CRH release was examined in cultured human syncytiotrophoblasts. CRH secretion and intracellular concentrations of cGMP, calmodulin-dependent protein kinase (CaM-PK), protein kinase-G (PKG), protein kinase-C, and cAMP- dependent protein kinase holoenzyme were measured under basal conditions and after treatment with a depolarizing concentration of KCl and with SNP. The results showed that depolarization (3 h) increased CRH release 4-fold (from basal value of 5.16 +/- 0.65 to 19.31 +/- 4.46 fmol/10(6) cells); SNP (100 mumol/L) decreased both basal (0.42 +/- 0.21 fmol/10(6) cells) and KCl-stimulated CRH release (0.94 +/- 0.32 fmol/10(6) cells). KCl also increased the activity of CaM-PK in the cell membrane and both cytosolic and membrane PKG activity, whereas the activities of protein kinase-C and cAMP-dependent protein kinase holoenzyme were unchanged. SNP increased intracellular cGMP concentrations after 10, 60, and 180 min. Methylene blue (100 mumol/L), a guanylate cyclase inhibitor, blocked the inhibitory effects of SNP on CRH release. These results suggest that NO exerts inhibitory effects on both basal and KCl-stimulated CRH release from placental syncytiotrophoblasts through a cGMP-mediated pathway. In addition, as KCl-induced changes in the cell membrane were blocked by SNP, CaM-PK may be involved in KCl-stimulated CRH release. KCl may also sensitize the inhibitory pathway involved in the regulation of CRH release by increasing cellular PKG levels. The effects of KCl and SNP on CRH release are more complex than simple activation of CaM-PK and PKG activity, as other cellular signal transduction pathways are also modulated.

This article has been cited by other articles:

				R. Yang, X. You, X. Tang, L. Gao, and X. Ni Corticotropin-releasing hormone inhibits progesterone production in cultured human placental trophoblasts J. Mol. Endocrinol., December 1, 2006; 37(3): 533 - 540. [Abstract] [Full Text] [PDF]

				X. You, R. Yang, X. Tang, L. Gao, and X. Ni Corticotropin-Releasing Hormone Stimulates Estrogen Biosynthesis in Cultured Human Placental Trophoblasts Biol Reprod, June 1, 2006; 74(6): 1067 - 1072. [Abstract] [Full Text] [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]

				J. Robidoux, L. Simoneau, A. Masse, and J. Lafond Activation of L-Type Calcium Channels Induces Corticotropin-Releasing Factor Secretion from Human Placental Trophoblasts J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3356 - 3364. [Abstract] [Full Text]

				J. Robidoux, L. Simoneau, S. St-Pierre, A. Masse, and J. Lafond Characterization of Neuropeptide Y-Mediated Corticotropin-Releasing Factor Synthesis and Release from Human Placental Trophoblasts Endocrinology, August 1, 2000; 141(8): 2795 - 2804. [Abstract] [Full Text] [PDF]

				F. M. Reis, M. Fadalti, P. Florio, and F. Petraglia Putative Role of Placental Corticotropin-Releasing Factor in the Mechanisms of Human Parturition Reproductive Sciences, May 1, 1999; 6(3): 109 - 119. [Abstract] [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]

				K. Sun, K. Yang, and J. R. G. Challis Differential Regulation of 11 {beta}-Hydroxysteroid Dehydrogenase Type 1 and 2 by Nitric Oxide in Cultured Human Placental Trophoblast and Chorionic Cell Preparation Endocrinology, November 1, 1997; 138(11): 4912 - 4920. [Abstract] [Full Text] [PDF]