Stimulatory effect of norepinephrine on progesterone production by human first trimester placenta explants in vitro

Norepinephrine (NE) was investigated for its effect on progesterone secretion from 6-8 week gestation human trophoblast tissue cultured in serum-free medium. Norepinephrine (5 micrograms/ml) enhanced progesterone secretion significantly on the third day of treatment. The stimulatory effect of NE on progesterone production was abolished by the alpha 1-receptor specific antagonist prazosin (10(-4) M) (P < 0.05), but was not influenced by the alpha 2-receptor specific antagonist yohimbine (10(-4) M) and the beta 1-receptor specific antagonist atenolol (10(-4) M). On the other hand, the alpha-receptor agonist clonidine (10(-6) M) had a similar stimulatory effect on progesterone release but the effect was antagonized by both the alpha 1-antagonist prazosin and the alpha 2-antagonist 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. The effect of NE was blocked by the voltage-dependent calcium channel blocker nifedipine (100 microM) but not by the voltage-independent calcium channel blocker gadolinium chloride (GdCl3) (10 microM). In addition, anti-gonadotropin releasing hormone (GnRH) IgG (5 micrograms/ml) and GnRH antagonist, (D-Phe2, D-Trp6)-GnRH (10(-6) M) did not influence the stimulatory effect of NE on progesterone release. The results indicate that NE regulates progesterone production in human first trimester trophoblast tissue. The effect of NE was mediated by the alpha 1 receptors. Cyclic AMP and voltage-dependent calcium channel were involved in its action.