Estrogen and progesterone relax female guinea pig gallbladder strips by different signaling pathways

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 338-357-Steroid Hormone Actions
Basic/Translational
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-342
Loren W Kline*1 and Edward Karpinski2
1Univ of AB/ Fac of Med & Dentist, Edmonton, AB, Canada, 2University of Alberta, Edmonton, AB, Canada
Estrogen and progesterone (P) have inhibitory effects on the contractility of gastrointestinal smooth muscle, including the gallbladder.  This study investigated the effect of 17β-estradiol (E2), P, 17-hydroxyprogesterone (17P), and a P metabolite 20α-hydroxyprogesterone (20P) on contraction in female guinea pig gallbladder strips. P, 17P, 20P, and E2 each relaxed cholecystokinin octapeptide (CCK) induced tension; the relaxation was concentration-dependent.  The relaxation was observed after 1 min.  The rapidity of the response suggested that it was nongenomic.  E2 and P had a similar effect on KCl-induced tension.  P relaxed CCK-induced tension more than either 17P or 20P.  Treatment of the strips with PKA inhibitor 14-22 amide mystrolated (PKA-IM) had no significant effect on E2-induced relaxation; however, PKA-IM significantly (p<0.01) decreased the amount of P-induced relaxation.  Treatment of the strips with 2-APB, a cell permeable inhibitor of IP3 induced Ca2+ release, produced a significant (p<0.001) increase in the amount of E2-induced relaxation when either CCK or KCl were used.  The use of 2-APB had no significant effect on P-induced relaxation.  Neither KT5823, a PKG inhibitor,  nor L-NMMA, NO synthase inhibitor,  had a significant effect on either the E2- or P-induced relaxation.  The use of PKC blockers significantly increased the amount of E2-induced relaxation, but significantly reduced the amount of P-induced relaxation. When either E2 or P were added to the chambers 3 min prior to either CCK or KCl, a significant decrease (p<0.001) in the amount of tension generated was observed.  The P-induced relaxation is mediated by the PKA/cAMP and PKC second messenger systems as well as inhibition of extracellular Ca2+ entry.  The E2-induced relaxation is mediated by the inhibition of extracellular Ca2+ in female guinea pig gallbladder strips.

Nothing to Disclose: LWK, EK

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: The Fund for Dentistry, University of Alberta.