Temporal effects of progesterone inhibition of occupied nuclear oestrogen receptor retention in the rat uterus

Previous studies have shown that progesterone rapidly inhibits retention of uterine nuclear oestrogen receptor in several mammalian species. This effect of progesterone may constitute a general mechanism by which progesterone modulates oestrogen action. The objective of the present study was to examine the temporal pattern of progesterone inhibition of retention of occupied nuclear oestrogen receptors in the rat uterus at various sustained serum concentrations of progesterone. Silicone elastomer implants (1 cm) packed with crystalline oestrogen were placed s.c. in the flank region of ovariectomized adult rats. Twenty-four hours after placement of the implants, animals were either injected s.c. with 5 mg progesterone in corn oil every 24 h, treated with 2 x 5 cm implants of progesterone, or treated with 1 x 5 cm silicone elastomer implants of progesterone. Serum concentrations of progesterone at the time of necropsy were 0.47 +/- 0.02, 0.18 +/- 0.02 and 0.10 +/- 0.01 mumol/l respectively. Control animals were given oestrogen implants alone and had a serum progesterone level of 0.03 +/- 0.01 mumol/l. Occupied nuclear oestrogen receptor and cytosolic oestrogen and progesterone receptor levels (pmol/uterus) were measured between 0 and 48 h following progesterone treatment. Cytosolic progesterone receptor levels were suppressed similarly in all progesterone-treated groups compared with controls given oestrogen alone throughout the 48-h test period. Cytosolic oestrogen receptor levels were significantly suppressed at 12 h following progesterone treatment in all groups. Except for the highest (pharmacological) serum progesterone concentration, cytosolic oestrogen receptor exhibited a replenishment phase between 12 and 48 h.(ABSTRACT TRUNCATED AT 250 WORDS)