Table 1.
Studies of progesterone inhibition of OXTR signaling.
| Species | Citation | Major findings |
|---|---|---|
| Rodent | Putnam et al., 1991 | P and P metabolites rapidly inhibit contractions of rat uteri within 2 min of treatment |
| Effect of P not opposed by treatment with the PGR antagonist RU 486 | ||
| Grazzini et al., 1998 | P reduced rat uterine OT signaling without a change in Oxtr mRNA expression | |
| Inhibition due to a P-mediated decrease in OT binding capacity, not binding affinity | ||
| Occurred at the level of the plasma membrane | ||
| Specific and high affinity binding sites for P only in transfected CHO cells expressing Oxtr with high affinity | ||
| Regulated by the state of the G-protein coupling to the receptor | ||
| Ovine | Dunlap and Stormshak, 2004 | Isolated membrane fractions pre-incubated with P showed decreased OT binding, reversed by co-incubation with RU 486 |
| High affinity binding site for P | ||
| P, R5020 (synthetic progestin), RU 486, and OT all bind to the same site pre-exposure of membranes to P significantly increased the number of P binding sites | ||
| Bishop and Stormshak, 2006 | P binding to endometrial membranes is dose dependent | |
| Inhibition of both OT-induced IP3 accumulation and PGF2α release from ovine endometrial explants by P within hours of exposure | ||
| Bishop et al., 2008 | Rapid, specific inhibition of OXTR signaling by P in COS7 cells transfected with the ovine OXTR that lack PGRs | |
| P did not decrease specific binding of OT | ||
| No specific P binding sites in membranes of OXTR-transfected cells | ||
| Bovine | Bogacki et al., 2002 | P inhibited OT binding at all concentrations (20–0.002 μM) investigated |
| OT-induced intracellular calcium release and PGF2α secretion by bovine endometrial tissue explants in the presence of actinomycin D | ||
| Duras et al., 2005 | P as well as pregnenolone, 17β-hydroxyprogesterone, the PR antagonist onapristone, and testosterone at μM concentrations were all able to interfere with OT-stimulated PGF2α secretion and intracellular calcium release | |
| Davis et al., 2010 | P at μM concentration rapidly (within 1 h) inhibited OT-induced Ca2+ release from endoplasmic reticulum of small steroidogenic luteal cells, possibly via exclusion of cholesterol from the luteal cell plasma membrane | |
| Primate/Human | Burger et al., 1999 | μM concentration of P inhibited the signaling of several related GPCRs as well as the OXTR |
| Chanrachakul et al., 2005 | Within 20 min-1 h P decreased OT-induced contractility of term myometrium in a concentration dependent manner | |
| Maximal inhibition at 10 μM P |