STIMULATORY EFFECT OF NOREPINEPHRINE ON PROGESTERONE PRODUCTION BY HUMAN 1ST TRIMESTER PLACENTA EXPLANTS INVITRO

Norepinephrine (NE) was investigated for its effect on progesterone se cretion from 6-8 week gestation human trophoblast tissue cultured in s erum-free medium. Norepinephrine (5 mug/ml) enhanced progesterone secr etion significantly on the third day of treatment. The stimulatory eff ect of NE on progesterone production was abolished by the alpha1-recep tor specific antagonist prazosin (10(-4) M) (P<0.05), but was not infl uenced by the alpha2-receptor specific antagonist yohimbine (10(-4) M) and the beta1-receptor specific antagonist atenolol (10(-4) M). On th e other hand, the alpha-receptor agonist chlonidine (10(-6) M) had a s imilar stimulatory effect on progesterone release but the effect was a ntagonized by both the alpha1-antagonist prazosin and the alpha2-antag onist yohimbine. Further study showed that NE induced a significant in crease in cyclic adenosine monophosphate (cAMP) production by trophobl ast 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 muM) bu t not by the voltage-independent calcium channel blocker gadolinium ch loride (GdCl3) (10 muM). In addition, anti-gonadotropin releasing horm one (GnRH) IgG (5 mug/ml) and GnRH antagonist, (D-Phe2, D-Trp6)-GnRH ( 10(-6) M) did not influence the stimulatory effect of NE on progestero ne release. The results indicate that NE regulates progesterone produc tion in human first trimester trophoblast tissue. The effect of NE was mediated by the alpha receptors. Cyclic AMP and voltage-dependent cal cium channel were involved in its action.