title: Norepinephrine regulates human chorionic gonadotrophin production by first trimester trophoblast tissue in vitro.
abstract: The effect of norepinephrine (NE) upon human chorionic gonadotrophin (hCG) production by 6-8 week gestation placental explants has been investigated. NE (5 micrograms/ml) enhanced hCG secretion significantly from the second day of treatment. The stimulatory effect of NE on hCG secretion could be abolished by the alpha 1-receptor specific antagonist prazosin (10(-4) M) and partly diminished by the beta 1-receptor specific antagonist atenolol (10(-4) M), but was not influenced by the alpha 2-receptor specific antagonist yohimbine (10(-4) M). The involvement of the alpha-receptor in the regulation of hCG secretion was further confirmed by addition of the alpha-receptor agonist clonidine (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 non-specific 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 alpha 1 and partly by beta 1 receptors. Cyclic AMP, the PKC signal transduction pathway and the voltage-dependent calcium channels were involved in NE action.
authors.affiliation: State Key Laboratory of Reproductive Biology, Chinese Academy of Sciences, Beijing.
authors.forename: C Z
authors.initials: CZ
authors.lastname: Shi
authors.forename: L Z
authors.initials: LZ
authors.lastname: Zhuang
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001262:Atenolol / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000096:biosynthesis* / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D006801:Humans; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D006063:Chorionic Gonadotropin; D007546:Isoquinolines; D010879:Piperazines; D015016:Yohimbine; D007987:Gonadotropin-Releasing Hormone; D001262:Atenolol; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000242:Cyclic AMP; D011493:Protein Kinase C; D003000:Clonidine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin