Acute Antiprogestational Action of Estradiol in the Rabbit Uterus*

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Abstract
Concomitant long term administration of 17β- estradiol (E2) with progesterone (P) has been shown to modulate P action in a dual fashion; low doses of E2 slightly potentiate P action, while higher E2 concentrations are strongly inhibitory. To study temporal aspects of the latter property of E2 (inhibition of progestational response), a large iv dose of E2 (50 μg/kg BW) was given to rabbits at various time intervals ranging from 2 h before to 8 h after the administration of a single iv dose of P (5 mg/kg BW). All animals were killed 12 h after P injection. The progestational response was evaluated by measurements of the uteroglobin (Ugl) concentration in the uterine fluid and tissue cytosol by RIA and of Ugl-mRNA activity in uterine tissue by cell-free translation. Twelve hours post injection, P alone evoked a 15- to 25-fold increase in the luminal fluid Ugl concentration, an 8- to 16-fold increase in the tissue Ugl levels, and a 4- to 8- fold elevation in the Ugl-mRNA activity. E2 given at times ranging from 2 h before to as late as 6 h after P administration markedly blunted luminal fluid Ugl accumulation, while no effect was observed when E2 was administered more than 6 h after P. E2 also prevented P action on the Ugl content in the uterine tissue, and hence, decreased luminal fluid Ugl accumulation did not derive from diminished release of this protein from the endometrial cells. While the P-enhanced increase in the UglmRNA activity was partially inhibited by E2 administration up until 4 h after P treatment, later E2 injections did not modify this action of P. Collectively, these observations indicate that a large dose of E2 acutely inhibits progestational response in the rabbit uterus. Seemingly, this effect involves, at least in part, decreased accumulation of P-induced mRNA.

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