Progesterone down-regulation of nuclear estrogen receptor: A fundamental mechanism in birds and mammals

Abstract

Progesterone is known to selectively down-regulate nuclear estrogen receptor (Re) in the mammalian uterus, and this process is functionally related to embryo retention. It is unclear if this mechanism is operative in the chick oviduct, where egg retention dots not occur. We investigated the regulation of Re by progesterone in a mammalian model (proestrous hamster uterus) and an avian model (DES-primed chick oviduct), under the same assay conditions, in an effort to compare progesterone action in viviparous and oviparous species. Nuclear and cytosol estrogen receptor were measured with an assay employing pyridoxal 5′-phosphate (PLP). The PLP assay has the advantage of allowing exchange at low temperature, which results in improved receptor recovery, especially from the nuclear fraction. Parallel studies were done under two different hormonal settings, estrogen primed and estrogen + progesterone primed. Experiments were: (1) response of Re to acute progesterone treatment (5 mg progesterone, 4 hr) in estrogen-primed preparation, (2) time course of the Re down-regulation response (4, 8, and 12 hr after progesterone treatment), and (3) recovery of Re after progesterone withdrawal in estrogen + progesterone-primed preparation. Chick oviduct contained little cytosol Re (0.96 ± 0.32 pmol/g tissue) compared to hamster uterus (4.27 ± 0.15 pmol/g tissue), and progesterone treatment had no effect on cytosol Re levels in either species. Nuclear Re levels were similar for chick oviduct (2.68 ± 0.14 pmol/g tissue) and hamster uterus (2.64 ± 0.14 pmol/g tissue). Progesterone treatment reduced nuclear Re levels in both the hamster uterus and chick oviduct to about 50% of control levels. In the chick oviduct, down-regulation was transient, as evidenced by complete recovery of nuclear Re to control levels by 12 hr after progesterone administration. In the estrogen + progesterone-primed chick oviduct, nuclear Re increased within 6 hr after progesterone withdrawal and approached maximal levels by 12 hr. These data indicate that progesterone rapidly and selectively down-regulates the nuclear form of Re in the chick oviduct as in the hamster uterus. Thus, the regulation of Re by progesterone appears to be similar in the mammalian uterus and the chick oviduct, despite the basic differences in reproductive strategy between birds and mammals. This suggests that progesterone down-regulation of nuclear Re is a fundamental mechanism of progesterone action which is conserved in birds and mammals and is not restricted to organisms which exhibit egg or embryo retention.