NOREPINEPHRINE REGULATES HUMAN CHORIONIC-GONADOTROPIN PRODUCTION BY FIRST TRIMESTER TROPHOBLAST TISSUE IN-VITRO

The effect of norepinephrine (NE) upon human chorionic gonadotrophin (hCG) production by 6–8 week gestation placental explants has been investigated. NE (5 μg/ml) enhanced hCG secretion significantly from the second day of treatment. The stimulatory effect of NE on hCG secretion could be abolished by the α1-receptor sepcific antagonist prazosin (10−4 m) and partly diminished by the β1-receptor specific antagonist atenolol (10−4 m), but was not influenced by the α2-receptor specific antagonist yohimbine (10−4 m). The involvement of the α-receptor in the regulation of hCG secretion was further confirmed by addition of the α-receptor agonist chlonidine (10−6 m) which had a similar stimulatory effect on hCG release but the effect was antagonized by both prazosin and yohimbine. Further study showed that NE induced a significant increase in cyclic adenosine monophosphate (cAMP) production by trophoblast tissue. Cyclic AMP secretion in the NE-treated group was fivefold higher than that of the control group. Both the protein kinase C (PKC) specific activator 1-deoyl-2-acetyl-sn-glycerol (OAG) and the PKC nonspecific activator phorbol-12-myristate-13-acetate (PMA) had a stimulatory effect on hCG secretion, while the PKC inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H7) diminished the hCG secretion stimulated by NE. The effect of NE was blocked by the voltage-dependent calcium channel blocker nifedipine but not by the voltage-independent calcium channel blocker gadolinium chloride (GdCl3). On the other hand, anti-gonadotrophin releasing hormone (GnRH) IgG and the GnRH antagonist (D-Phe2, D-Trp6)-GnRH did not influence the stimulatory effect of NE on hCG release. The results indicate that NE regulates hCG production in human first trimester trophoblast tissue. The effect of NE was mainly mediated by α1 and partly by β1 receptors. Cyclic AMP, the PKC signal transduction pathway and the voltage-dependent calcium channels were involved in NE action. © 1993, Baillière Tindall Ltd. All rights reserved.