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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both estrogens and androgens have been shown to stimulate sex hormone binding globulin (SHBG) secretion in vitro in the hepatocellular carcinoma cell line, Hep G2, in contrast to the expected inhibition by androgens from in vivo studies. However, such in vitro stimulation was only demonstrated at high steroid doses, generally in serum-containing medium, with added Phenol Red. In the present study, Hep G2 cells were grown in serum-free medium, without Phenol Red, under the influence of testosterone (T) (0, 0.5-500 nM) and ethinyl estradiol (EE2) (0, 50 pM-500 nM). Levels of secreted SHBG and albumin were correlated with androgen receptors in cytosolic (ARc) and nuclear (ARn) fractions and with DNA levels. In the presence of increasing T levels, SHBG levels fell to 39% of control values at 5 nM T (P = 0.047), rising to 97% of control at 500 nM. Conversely, incubation with EE2 produced a rise in SHBG secretion of more than 100% at 0.5 nM (P less than 0.02) which was sustained to 50 nM (P less than 0.005). DNA levels did not change with the addition of testosterone or EE2, with the exception of a 15% reduction at 5 nM EE2 (P less than 0.05). Albumin levels in the medium were not significantly altered by either steroid. However, in response to T, androgen receptor (AR) levels were reduced in cytosolic (42% of control) and nuclear (22%) fractions at 5 nM, and these changes in ARc and ARn correlated with SHBG levels over the range of T concentrations (P = 0.04 and P = 0.017, respectively). Nuclear estrogen receptor (ER) increased over 10-fold at 5 and 50 pM EE2 (P less than 0.001) and maintained 50 nM (P less than 0.001). Cytosolic ER was reduced at 0.5 and 5 nM but recovered at 50 nM, correlating with SHBG levels (P less than 0.001). These findings are consistent with the hypothesis that estrogens and androgens regulate SHBG synthesis in man by direct, specific, probably receptor-mediated effects on hepatocytes. Hep G2 cells grown in serum-free medium are a suitable experimental system for further study of this phenomenon.
J Steroid Biochem Mol Biol 1990 Dec 10
PMID:Estrogen and androgen regulation of sex hormone binding globulin secretion by a human liver cell line. 227 57

Estrogen-receptor complex activates the genes coding for the egg yolk protein precursor vitellogenin in hepatocytes of oviparous vertebrates, while oocyte vitellogenin genes are unresponsive to the hormone. Localization of [3H]steroid hormones (estradiol, progesterone, testosterone, and dexamethasone) was assayed in 10% trichloroacetic acid-precipitated dissected Xenopus oocytes (germinal vesicle vs. the rest of the oocyte). Whether hormones were introduced by incubation in the medium surrounding the oocytes or by injection of an equivalent amount into the oocyte cytoplasm, all hormones partitioned into the nucleus at equivalent levels (approximately 5%), reflecting that portion of the oocyte volume occupied by its nucleus. Therefore, intracellular receptors for these hormones were not detectable. Subsequently, we introduced a species-heterologous estrogen receptor into the Xenopus oocyte via a recombinant plasmid containing the coding sequence for the human estrogen receptor (HER) housed in a vector that ensures highly efficient transcription and translation of inserted sequences. HER synthesis was directed from injected plasmid (2 ng/oocyte germinal vesicle) as shown by [35S]methionine incorporation into newly synthesized proteins; however, vitellogenin was not synthesized under these conditions. When HER plasmid-injected oocytes were incubated in [3H]estradiol, they translocated to the nucleus 38% of the radiolabeled estradiol taken up by the cells, compared to 5% nuclear localization for vector-injected controls. Therefore, although the oocyte can readily transcribe and translate HER sequences as well as appropriately partition the completed protein in the nuclear compartment, the endogenous, potentially estrogen-responsive vitellogenin genes of the oocyte are not expressed.
Mol Endocrinol 1990 Apr
PMID:Expression and translocation of cloned human estrogen receptor in the Xenopus oocyte does not induce expression of the endogenous oocyte vitellogenin genes. 228 Jul 76

In vitro exposure of estrogen receptor-negative (ER-) EVSA-T human breast cancer cells to insulin and/or estradiol had no effect on cell cycle distribution, in contrast to a 3-5-fold increase in the percentages of cells in the S-phase of the cell cycle in the ER+ MCF-7 cell line. Estrogen pretreatment of MCF-7 cells followed by incubation with doxorubicin resulted in an augmented inhibition of cell growth compared to unstimulated controls. This delay in growth was accompanied by a decrease in the percentages of cells actively synthesizing DNA, and by an augmented percentage of cells exhibiting a G2M-amount of DNA at the end of a 6-9 day period of culture in complete growth medium.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Manipulation of cell cycle kinetics: influence on the cytotoxicity of doxorubicin in human breast cancer cells. 228 83

Antileukoproteinase (ALP) is a low mol wt mucosal secretory protein which, in human tissues, inhibits the activities of the neutral serine lysosomal proteinases elastase and cathepsin-G. In this study a number of recombinant cDNA clones corresponding to porcine ALP (pALP) were isolated from a cDNA library prepared from porcine endometrial poly(A)+ RNAs. The combined nucleotide sequences of the cDNA clones, representing the entire pALP mRNA sequence, are approximately 600 nucleotides long and encode a protein of 114 amino acids. The deduced amino acid sequence of pALP is 68% similar in primary structure to that of human ALP, is cysteine and proline rich, and exhibits a two-domain structure which, in the human protein, is involved in binding trypsin/cathepsin-G and elastase, respectively. However, pALP appears to lack the internal signal sequence of the corresponding human protein. Northern blot analysis of uterine RNAs using pALP cDNAs as probe demonstrated a single mRNA species approximately 0.8 kilobase in length. Uterine expression of pALP mRNA was highest in mid- and late pregnancy and very low or undetectable in early pregnancy. Estrogen and progesterone increased the levels of uterine pALP mRNA in prepubertal gilts, but not to the levels obtained at mid- and late gestation. pALP mRNA was also abundant in adult pig lung, where its expression was constitutive. Lower levels of pALP were found in fetal and neonatal lung and small intestine and in maternal cervix, spleen, and small intestine. Our study on the molecular cloning and analysis of pALP mRNA represents the first report on the porcine proteinase inhibitor and extends the identification of pregnancy-associated uterine proteins, which may play important functions in embryo or fetal development. The control of expression of pALP mRNA, which is distinct from those of other porcine uterine proteins studied to date, should provide additional insights into the mechanisms of regulation of uterine secretory activity.
Mol Endocrinol 1990 Aug
PMID:Complementary DNA cloning and regulation of expression of the messenger RNA encoding a pregnancy-associated porcine uterine protein related to human antileukoproteinase. 229 19

Kidney androgen-regulated protein (KAP) gene expression is under androgenic control in the epithelial cells of the proximal convoluted tubule in the mouse kidney. In Tfm/Y androgen receptor-deficient mice, KAP mRNA was detected by in situ hybridization in a subpopulation of these cells only in the S3 segment of the proximal tubules in the outer medulla. Treatment of Tfm/Y animals with testosterone caused a partial induction of KAP mRNA levels, while dihydrotestosterone had no effect. These data suggested that the androgen receptor-independent induction of KAP gene expression in these animals was mediated by an estrogenic metabolite of testosterone, since dihydrotestosterone cannot be aromatized to an estrogenic form. Estrogen treatment of Tfm/Y mice caused an increase in KAP gene expression similar to that observed with testosterone. However, ovariectomy of normal female mice did not eliminate KAP gene expression in the S3 cells and, in fact, resulted in a slight increase. Adrenalectomy in combination with castration had no effect on KAP mRNA levels in S3 cells. However, hypophysectomy alone completely eliminated this cell-specific component of KAP gene expression. These results indicate that KAP gene expression is subject to cell-specific regulation in different segments of the proximal tubule and that this regulation is mediated by hormones of both gonadal and pituitary origin.
Mol Endocrinol 1990 Aug
PMID:Cell-specific expression of kidney androgen-regulated protein messenger RNA is under multihormonal control. 229 28

The distribution of estrogen and progesterone receptors (ER and PR, respectively) was studied immunohistochemically in the chick oviduct. Estrogen receptor immunoreactivity was found only in the nuclei of glandular epithelial cells. Progesterone receptor was found in the nuclei of glandular and luminal epithelia, stroma, smooth muscle cells and in the mesothelium. The dissimilar distribution of ER and PR suggests that either ER concentration in the luminal epithelium and smooth muscle is very low (below the sensitivity of ER immunostaining) or that estrogens control their PR synthesis indirectly via ER in glandular cells. A known estrogen-inducible protein, ovalbumin, was localized in the same glandular epithelial cells as ER. A progestin-inducible protein, avidin, was found in part of the luminal and glandular epithelium cells but not in other PR-positive cell types. This indicates the importance of cellular differentiation in the regulation of avidin synthesis. Estrogen and progesterone administration had effects also on ER and PR immunoreactivity. Estrogen and progesterone administrations for 24 h decreased markedly the immunoreactivity of their receptors. The decrease in receptor immunoreactivity is most likely due to a transient loss of immunoreactive receptor protein, since the antibodies (H222, PR6) react both with transformed (4 S) and non-transformed (8 S) receptor forms. At the subcellular level, PR was localized in the chromatin by immunoelectron microscopy. Progestin administration seemed to decrease PR immunoreactivity especially in the heterochromatin area, suggesting that conformational chromatin rearrangements occur during down-regulation of PR.
Mol Cell Endocrinol 1990 Mar 05
PMID:Distribution of estrogen and progesterone receptors and steroid-regulated gene products in the chick oviduct. 232 29

Estrogen induces DNA synthesis to a lesser degree, but with similar kinetics compared to insulin-like growth factors when added to quiescent MCF7 human breast cancer cells. Moreover, this steroid rapidly induces expression of the growth-related c-fos and c-myc protooncogenes. The induction was shown to be a direct effect, independent of protein synthesis. These results demonstrate that no growth factor production is involved in estrogen-induced protooncogene expression, and that these direct effects on gene expression may be an important step in estrogen-induced mitogenesis.
Mol Cell Endocrinol 1989 Jul
PMID:Direct effects of estrogen on c-fos and c-myc protooncogene expression and cellular proliferation in human breast cancer cells. 250 74

The present study examined 1) whether the estrogen-regulated destabilization of albumin mRNA occurs in the nuclear or extranuclear fraction of the liver cell, and 2) whether the selective posttranscriptional regulation of albumin mRNA stability might result from covalent changes introduced in the processing or polyadenylation of the primary transcript. The disappearance of albumin mRNA after estrogen is restricted to the extranuclear fraction of the cell. Transient changes in steady state levels of the mature nuclear transcript were observed that mirrored the transient estrogen-induced changes previously reported for albumin gene transcription. When assayed 24 h after estrogen (when albumin RNA is virtually undetectable in the extranuclear fraction) the steady state levels of both the primary and mature albumin transcripts found in the nucleus were the same as observed in control animals. Estrogen had no effect on the splicing or selection of polyadenylation sites on the 3'-UTR as determined by high resolution gel analysis of the 3'-UTR and DNA sequencing of cDNA clones isolated from a liver library from an estrogen-treated male Xenopus. Most eukaryotic mRNAs have poly(A) tracts several hundred residues in length, and recent studies have demonstrated that a change in the stability of a number of mRNAs correlates directly with the degree of polyadenylation. Albumin contrasts sharply with this, first because it has an exceptionally short poly(A) tail of 17 residues, and second because the degree of polyadenylation is totally unrelated to its destabilization in response to estrogen. These findings indicate that a unique pathway is involved in the regulation of albumin RNA stability by estrogen in Xenopus.
Mol Endocrinol 1989 May
PMID:Extranuclear estrogen-regulated destabilization of Xenopus laevis serum albumin mRNA. 254 54

Estrogen and progesterone or estrogen and glucocorticoid receptors functionally cooperate in gene activation if their cognate binding sites are close to one another. These interactions have been described as synergism of action of the steroid receptors. The mechanism by which synergism is achieved is not clear, although protein-protein interaction of the receptors is one of the favorite models. In transfection experiments with receptor expression vectors and a reporter gene containing estrogen and progesterone-glucocorticoid receptor binding sites, we have examined the effects that different portions of the various receptors have on synergism. N-terminal domains of the chicken progesterone and human glucocorticoid receptors, when deleted, abolished the synergistic action of these receptors with the estrogen receptor. Deletion of the carboxy-terminal amino acids 341 to 595 of the estrogen receptor produced a mutant receptor that could not trans-activate on its own. This mutant receptor did not affect the action of the glucocorticoid receptor but functioned synergistically with the progesterone receptor. We therefore conclude that the synergistic action of the receptors for estrogen and progesterone is mechanistically different from the synergistic action of the receptors for estrogen and glucocorticoid.
Mol Cell Biol 1989 Dec
PMID:Different regions of the estrogen receptor are required for synergistic action with the glucocorticoid and progesterone receptors. 258 23

Sex steroids are major regulators of PRL receptor expression in rat liver. Using a probe encoding the rat PRL receptor we have studied receptor mRNA levels in female rat liver during ontogeny and in response to estrogen treatment. Steady state mRNA levels were determined by Northern blot and densitometric analysis. Messenger RNA levels have been compared to the number of binding sites, which was assessed by Scatchard analysis of [125I]ovine PRL binding in membrane preparations. Our results show that steady state mRNA and binding levels of PRL receptors are both regulated by development and estrogens, but that binding does not exactly parallel mRNA levels. From the developmental stages of prepuberty to adult, receptor numbers increase 8-fold, whereas mRNA levels increase 3-fold. Estrogen treatment stimulates receptor levels 6-fold, but mRNA levels are only increased 3-fold. These results suggest that PRL receptor gene expression in rat liver is regulated at the transcriptional or posttranscriptional level as well as at the translational level.
Mol Endocrinol 1989 Jun
PMID:Multiple regulation of prolactin receptor gene expression in rat liver. 273 54


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