Ontogeny of Steroid Receptors in the Reproductive System

Pasqualini, Jörge R.; Sumida, C.

doi:10.1016/s0074-7696(08)60251-x

Cited by 14 publications

(7 citation statements)

References 153 publications

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“…While a number of proteins interacting with the ER have been identified and studied, the mechanism by which this receptor modulates gene transcription is still unclear. The ER has been shown to be present in a large number of different tissues (13,14,29,56). While some of the factors associated with the receptor are ubiquitously expressed, others may be cell-specific FIG.…”

Section: Discussionmentioning

confidence: 99%

POU Transcription Factors Brn-3a and Brn-3b Interact with the Estrogen Receptor and Differentially Regulate Transcriptional Activity via an Estrogen Response Element

Budhram-Mahadeo

Parker

Latchman

1998

Molecular and Cellular Biology

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The estrogen receptor (ER) modulates transcription by forming complexes with other proteins and then binding to the estrogen response element (ERE). We have identified a novel interaction of this receptor with the POU transcription factors Brn-3a and Brn-3b which was independent of ligand binding. By pull-down assays and the yeast two-hybrid system, the POU domain of Brn-3a and Brn-3b was shown to interact with the DNA-binding domain of the ER. Brn-3-ER interactions also affect transcriptional activity of an ERE-containing promoter, such that in estradiol-stimulated cells, Brn-3b strongly activated the promoter via the ERE, while Brn-3a had a mild inhibitory effect. The POU domain of Brn-3b which interacts with the ER was sufficient to confer this activation potential, and the change of a single amino acid in the first helix of the POU homeodomain of Brn-3a to its equivalent in Brn-3b can change the mild repressive effect of Brn-3a to a stimulatory Brn-3b-like effect. These observations and their implications for transcriptional regulation by the ER are discussed.Transcriptional regulation by the complex interaction of different classes of transcription factors allows a limited number of proteins to elicit diverse effects on gene expression, depending on the expression of other proteins, such as tissue-specific factors and signals which may influence their interactions (reviewed in references 39, 40, 59, and 68 and references therein). We were interested in looking at proteins which interact with the transcription factors Brn-3a and Brn-3b and modulate the regulation of gene expression by these proteins. These two proteins belong to the POU (Pit-Oct-Unc) family of transcription factors (21,25,26,42,66,70,73,76). Members of this class of transcription factors are defined on the basis of the common POU domain, which consists of two highly conserved regions, the POU-specific domain and the POU homeodomain, which are separated by a poorly conserved linker region. The POU domain acts as the DNA-binding domain which recognizes and binds specific DNA sequences present in target gene promoters but is also involved in protein-protein interactions (3,72,73). There are three known members of the Brn-3 family of transcription factors, namely, Brn-3a (also known as Brn-3.0) (21, 42, 65), Brn-3b (also called Brn-3.2) (42, 65, 70), and Brn-3c (also known as Brn-3.1) (21, 52), which are encoded by different genes (65, 77). Furthermore, different isoforms of Brn-3a and Brn-3b which result from alternative splicing of the genes encoding these two proteins have been identified (21,43,65,70).The Brn-3 proteins show restricted homology outside the conserved carboxyl-terminal POU domain and the amino-terminal POU IV box (21,65,70). Since the studies reported here were carried out with Brn-3a and Brn-3b, references to Brn-3 proteins will pertain to observations with Brn-3a or Brn-3b and not Brn-3c. Sequence differences between Brn-3a and Brn-3b proteins are paralleled by different effects on promoters which contain binding sites recog...

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Section: Discussionmentioning

confidence: 99%

POU Transcription Factors Brn-3a and Brn-3b Interact with the Estrogen Receptor and Differentially Regulate Transcriptional Activity via an Estrogen Response Element

Budhram-Mahadeo

Parker

Latchman

1998

Molecular and Cellular Biology

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“…& Sumida 1986). The present information is of particular interest because in the rat during gestation, large quantities (1-3 g/1) of -fetopro¬ tein are present in the plasma of pregnant rats (Gitlin & Boeman 1967), and it is generally be¬ lieved that -fetoprotein, by binding specifically estrogens and with high affinity, can block the biological response of the hormone.…”

Section: Discussionmentioning

confidence: 99%

Effect of estradiol on the progesterone receptor and on morphological ultrastructures in the fetal and newborn uterus and ovary of the rat

Nguyen¹,

Hatier²,

Jeanvoine³

et al. 1988

Acta Endocrinologica

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The effect provoked by estradiol after administration to pregnant rats (1 mg per day) was studied in fetal and newborn uteri and ovary. Estrogen receptors are found in the fetuses of non-treated animals.Their number (in fmol/mg DNA,\ m=+-\ sd) in the fetal uterus (total sites, cytosol + nuclei) was at the age of 18 days: 63 \ m=+-\15; at 20 days 101 \ m=+-\13; and in the 24-h-old newborn; 415 \ m=+-\ 120. The respective values in the ovary were: 105 \ m=+-\ 25; 520 \m=+-\ 60 and 410 \m=+-\ 190. Estradiol stimulated significantly the progesterone receptor in the fetal uterus at 20 days old. The progesterone receptor (in fmol/mg DNA, \m=+-\ sd) which was 97 m=+-\17 in the non-treated animals, increased to 790 m=+-\90 in the E2-primed animals. Newborns, 24-h-old, had no detectable progesterone receptor, but in the E2-treated animals the value increased to 1210 \m=+-\120. In the fetal ovary of non-treated animals, progesterone receptor at the age of 18 days is: 90 \m=+-\19; at 20 days 132 \ m=+-\ 47, and in the newborns 260 \ m=+-\ 67; in the E2-treated animals, the values are respectively 330 \ m=+-\ 49; 865 \m=+-\ 78 and 1280 \m=+-\ 307. In the fetal uteri of E2-treated animals, histological and ultrastructural studies showed an increase in the size of the uterine horn, the height of the epithelial cells, and stromal cell differentiation. It is suggested that, as was extensively demonstrated in the fetal compartment of the guinea-pig, the machinery for estrogen responses operates also during fetal development of the rat.The rat was the first animal species in which estrogen receptors were detected and character¬ ized (Jensen & Jacobson 1962). In this and other studies, immature or adult ovariectomized rats were mostly used. It is also well known that progesterone receptor is a function of estrogen activity (O'Malley et al. 1971). More recently, the presence of estrogen receptor and the biological response to estrogens were extensively demon¬ strated in different target tissues during fetal development of the guinea pig (Pasqualini et al. 1976;Pasqualini & Nguyen 1980). To our knowl¬ edge there is limited information available at present concerning the presence in the rat of estrogen receptor and biological responses to estrogens in the fetal uterus during fetal develop¬ ment. One reason for this is the presence in the fetal and maternal plasma of this species of huge quantities of rx-fetoprotein, a protein which binds estrogens in this animal species, with high affinity and specificity (Soloff et al. 1971;Nunez et al. 1971). It is also generally accepted that the inter¬ action of this protein with the circulating estro¬ gens can block the action of the hormone.In the present study we investigated the pres¬ ence of estrogen receptor in the fetal uterus of the rat, as well as the biological response to stimula¬ tion of the progesterone receptor in the fetal uterus and ovary after administration of estradiol to the maternal compartment of the pregnant rat.The effect was also studied in the uterus and ovary of newborn ...

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“…In several species, estrogen treatment of fetal and neonatal females results in the stimulation of increased uterine levels of nucleic acid (136,145), protein synthesis (146), ornithine decarboxylase (147), progesterone receptor (148), and cellular proliferation (145,149,150). However, a full biological response to estradiol in terms of maximum increases in uterine weight is not possible in the neonatal uterus, and can be observed only after the animal approaches weaning age (146).…”

Section: Reproductive Tract Phenotypes Of the Femalementioning

confidence: 99%