Developmental regulation of the estrogen receptor and the estrogen responsiveness of five yolk protein genes in the avian liver.

Abstract

The magnitude of the expression of five yolk protein genes in the avian liver in response to exogenous estradiol is shown to be developmentally regulated. Though each of these yolk protein genes gains the capacity to respond to estradiol during embryonic development, we demonstrate that maximal responses for the different genes are achieved at distinct ages between 1 and 6 weeks after hatching. This observation prompted us to look for possible correlations between yolk protein gene expression and changes in the expression of estrogen receptors that might also occur after hatching. We discovered that indeed the maximal level of nuclear estrogen receptors (assayed following the administration of estradiol) increases progressively over this same period of development from "1000 receptors per cell at 1 week after hatching to %3500 receptors per cell at 6 weeks after hatching. The latter number represents the fully mature state, as comparable levels of receptors are present in the livers of egg-laying hens. Thus, though increases in the expression of estrogen receptors during embryonic liver development have previously been reported, our results indicate that the changes that occur after hatching are quantitatively far more significant to the developmental program for this transcription factor.The vitellogenic response in the avian liver provides an excellent model system in which to study the molecular mechanisms that underlie the developmental, steroid, and tissuespecific regulation of gene expression. In normal development three vitellogenin genes and an apolipoprotein gene, which collectively account for the bulk of the yolk proteins, are expressed exclusively in the livers of hens during periods of egg laying. The expression of this set of yolk genes is dependent on the elevated level of circulating estrogen that accompanies egg laying and is thus coordinated with the complementary production of egg white proteins in the oviduct. The complete set of yolk genes can be induced in the livers of both males and females, however, by simply injecting estradiol. This de novo induction is effected at the transcriptional level (ref. 1; unpublished results) and is accentuated by an increase in yolk message stability in the presence of estradiol (2). The capacity of these genes to respond to estradiol is demonstrable by day 9 of embryonic development (ref. 3; unpublished results) and thus reflects an early tissue-specific commitment event (4).The fact that there is an extended developmental period during which the vitellogenin and apolipoprotein genes have the potential to respond to estradiol but are transcriptionally silent in their normal state has afforded the opportunity to examine in detail the kinetics of accumulation of yolk protein (5)(6)(7)(8) and RNA (9-11) following primary and secondary injections of estradiol. Studies of this sort have revealed that birds retain a "memory" of their primary response, as evidenced by the fact that secondary presentations of estradiol elicit the more rapid accumulation of...

In vivo estrogen induction of hepatic estrogen receptor mRNA and correlation with vitellogenin mRNA in rainbow trout

“…HOWever, in the rainbow trout, further studies of primary and secondary inductions are necessary to determine the kinetics of stimulation and to confirm that there is no variation in sensitivity of ER and Vg genes after hatching, in contrast to the results obtained with the chicken (Evans et al, 1987). Further studies are also necessary to determine if the presence of ER is sufficient during early embryogenesis for Vg gene induction or if another mechanism such as chromatin structure modification is also necessary (Weisbord, 1982).…”

“…As rtER mRNA and nuclear ER levels recover to basal values 3 weeks after E, treatment, we decided to investigate whether the Vg gene in rainbow trout was secondarily induced with a memory effect as described for Vg genes in Xenqus and chicken (Tata and Smith, 1979;Shapiro, 1982;Evans et al, 1987). Male rainbow trout (600-900 g) were first injected with E, (1.5 mg/kg) or with the same amount of solvent.…”

“…Secondary induction is defined by the disappearance of the lag period and the increase in the accumulation rate of Vg mRNA revealing that liver cells retain a 'memory' of the primary stimulation (Tata and Smith, 1979;Shapiro, 1982;Evans et al, 1987). This memory effect persists for as long as 6 months and is passively maintained through cell division (Burch and Evans, 1986).…”

The slower the better: how sperm capacitation and acrosome reaction is modified in the presence of estrogens

“…They regulate cell function through ERs (ERA and ERBb; Lubahn et al 1993), which belong to a superfamily of ligand-activated transcription factors (Evans et al 1987) and they are localized in the cytoplasm and nucleus of somatic and germinal cells. The nuclear receptors activate gene transcription by binding to DNA regulatory sequences (Hall et al 2001).…”

Developmental regulation of specific protein interactions with an enhancerlike binding site far upstream from the avian very-low-density apolipoprotein II gene.

“…Although dormant in roosters, chicks, and embryos, these genes can be activated in birds of either sex without a requirement for DNA replication (25). Despite this fact, the liver displays a propagatable, estrogen-priming effect that is reflected by a long-lasting alteration in the kinetics with which the genes respond to restimulation with the hormone (10,15,17,26,30).…”