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

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Abstract
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 × 5 cm implants of progesterone, or treated with 1 × 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 μmol/l respectively. Control animals were given oestrogen implants alone and had a serum progesterone level of 0·03 ± 0·01 μmol/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. Although pharmacological levels of serum progesterone (0·47± 0·02μmol/l) significantly suppressed the level of occupied nuclear oestrogen receptor at 12 h, the level increased subsequently at 24 and 36 h and was equivalent to the control value (oestradiol alone) by 48 h. At a mean serum concentration of 0·18 ± 0·02 or 0·10 ± 0·01 μmol/l, the level of occupied nuclear oestrogen receptor was also suppressed significantly at 12 h, but to a lesser degree. These results show that progesterone decreases the concentration of occupied nuclear oestrogen receptor in the rat uterus and that the duration and extent of suppression of occupied nuclear oestrogen receptor is related to the serum progesterone concentration. Journal of Endocrinology (1989) 121, 101–107