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

Progesterone receptors (PRs) mediate the actions of progestin hormones and play important roles during the reproductive cycle and pregnancy. Since PR expression is known to be regulated by estrogen, we have undertaken studies to examine the mechanisms underlying this regulation. We have identified multiple distinct regions of the rat PR gene, widely spaced and spread throughout the 5'-flanking region, the 5'-untranslated region, and the first exon (between -2264 and +2241), that can form a strong estrogen-responsive enhancer when linked together. Estrogen-responsive activities for two of the regions in isolation (+461/+636 and +2176/+2241) were demonstrated in one or more homologous or heterologous promoter contexts. The contributions of the other regions (-2264/-1970, -1167/-957 and +2088/+2110) to the overall activity of the assembled enhancer were cryptic in that they were only observed in the context of the other PR gene fragments, not in isolation. We identified four weak, but functional, imperfect estrogen response elements (EREs) in these regions of the PR gene, each differing from the consensus by 2 base pairs. In addition, we identified four ERE half-sites in the PR gene, three of which are paired (i.e. < 150 base pairs away) with the EREs in the estrogen-responsive regions. Competitive gel shift assays demonstrated weak, but detectable, binding of estrogen receptor to the EREs. Of note, the estrogen-responsive enhancer assembled from the five regions of the PR gene exhibited promoter specificity; it conferred estrogen responsiveness of the distal PR gene promoter, but it failed to enhance the endogenous estrogen responsiveness of the proximal PR gene promoter. The positioning of response elements in the rat PR gene, which we show to be unique among steroid hormone-regulated genes, may have functional consequences for the regulation of the magnitude and timing of PR gene expression by estrogen.
Mol Endocrinol 1994 Aug
PMID:Identification of multiple, widely spaced estrogen-responsive regions in the rat progesterone receptor gene. 799 37

Microtubule proteins were isolated by a temperature-dependent assembly-disassembly method from brain tissue of for cold-temperature fish; one fresh water fish (Oncorhynchus mykiss), and three marine fish (Labrus berggylta, Zoarces viviparus and Gadus morhua). The alpha-tubulins from all four fish species were acetylated. The alpha-tubulins from the marine fish were composed of a mixture of tyrosinated and detyrosinated tubulin, while the fresh water fish tubulin only reacted with an antibody against detyrosinated tubulin. The isolated microtubules had a similar MAP composition. A 400 kD protein and a MAP2-like protein were found, but MAP1 was missing. All microtubules disassembled upon cooling to 0 degrees C. In spite of these common characteristics, the assembly of microtubules from Labrus berggylta was inhibited by colchicine and calcium, in contrast to the assembly of microtubules from Oncorhynchus mykiss and Zoarces viviparus. For the latter, colchicine was not completely inhibitory even at a concentration as high as 1 mM, and calcium induced the formation of both loosely and densely coiled ribbons. The effects of calcium and colchicine on microtubules from Oncorhynchus mykiss and Zoarces viviparus were modulated by either fish or cow MAPs, indicating that the effects are due to intrinsic properties of the fish tubulins and not the MAPs. In view of these findings, our results suggest that there is no correlation between colchicine sensitivity, inability of calcium to inhibit microtubule assembly, and acetylation and detyrosination.
Mol Cell Biochem 1994 Jan 26
PMID:Different stability of posttranslationally modified brain microtubules isolated from cold-temperate fish. 802 93

We have previously shown that estrogen and progestins regulate both cellular proliferation and transforming growth factor (TGF) expression in human endometrial adenocarcinoma cells in vitro. In the current study we examined the regulation of TGF-alpha and -beta 1 expression in endometrial adenocarcinoma xenografts. Four human endometrial adenocarcinoma cell lines were inoculated into female BALB/c nude mice. Administration of 17 beta-estradiol (E2) increased tumor size in intact mice inoculated with Ishikawa, HEC-50 and HEC-1B cells but inhibited growth of HEC-1A xenografts. 4-Hydroxy tamoxifen (OH-Tam) had similar effects to E2 in animals carrying Ishikawa and HEC-1A cell xenografts but had no significant effect on growth of HEC-50 or HEC-1B xenografts. In intact mice inoculated with OH-Tam pellets and Ishikawa cells, the tumors were larger and had lower levels of TGF-alpha mRNA than in untreated or E2 treated mice. In mice carrying Ishikawa, HEC-50 and HEC-1B cell xenografts none of the hormones or agents tested altered TGF-beta 1 mRNA levels. In contrast, both E2 and OH-Tam significantly increased xenografts TGF-beta 1 mRNA levels in HEC-1A xenografts as well as significantly reduced tumor size. Medroxyprogesterone acetate (MPA) had no effect on tumor size of Ishikawa, HEC-1A and HEC-1B cell cell xenografts but significantly increased the size of HEC-50 xenografts. MPA significantly reduced TGF-alpha expression in Ishikawa cell xenografts but had no effect in the other cell xenografts. MPA had no effect on TGF-beta 1 expression in any of the xenografts. These observations demonstrate a discordance between the hormonal effects on TGF expression and cellular proliferation and argue against a major role for the TGFs in regulation of human endometrial adenocarcinoma cell proliferation in vivo.
J Steroid Biochem Mol Biol 1994 Jul
PMID:Hormonal regulation of proliferation and transforming growth factors gene expression in human endometrial adenocarcinoma xenografts. 804 28

Progesterone receptors (PgR) of human breast cancer T47-D cells grown in an estrogenic environment (presence of phenol red, natural estrogens of foetal calf serum and insulin) were found to be present in considerable amounts (1-3 pmol/mg protein and 20 pmol/mg DNA), and to specifically bind progestins with a high affinity characterized by a Kd around 3 nM for ORG2058, and 4 nM for nomegestrol acetate (NOM; 17 alpha-acetoxy-6-methyl-19-nor-pregna-4,6-diene-3, 20-dione), when measured under equilibrium conditions. Both compounds formed an highly stable ligand-receptor complex with a dissociation constant (k-1) around 1 x 10(-5) s-1. At high pharmacological concentrations, NOM, ORG2058 and other synthetic progestins including promegestone (R5020), medroxy-progesterone acetate and norethindrone acetate (NOR), induced a dose-dependent inhibition of cell proliferation as measured by [3H]thymidine incorporation. Dexamethasone, which did not bind to PgR, did not reproduce this inhibitory effect. NOM, R5020 and NOR treatments of T47-D cells at concentrations around Kd resulted in an 80% decrease in PgR content. Our data on NOM as compared to other progestins are consistent with their antiproliferative effects on human breast cancer cells grown in estrogenic conditions.
J Steroid Biochem Mol Biol 1994 Jul
PMID:Inhibition by nomegestrol acetate and other synthetic progestins on proliferation and progesterone receptor content of T47-D human breast cancer cells. 804 31

MAP (mitogen-activated protein) kinases are serine/threonine protein kinases and mediate intracellular phosphorylation events linking various extracellular signals to different cellular targets. MAP kinase, MAP kinase kinase and MAP kinase kinase kinase are functional protein kinase units that are conserved in several signal transduction pathways in animals and yeasts. Isolation of all three components was also shown in plants and suggests conservation of a protein kinase module in all eukaryotic cells. In plants, MAP kinase modules appear to be involved in ethylene signaling and auxin-induced cell proliferation. Therefore, coupling of different extracellular signals to different physiological responses is mediated by MAP kinase cascades and appears to have evolved from a single prototypical protein kinase module which has been adapted to the specific requirements of different organisms.
Plant Mol Biol 1994 Feb
PMID:MAP kinases: universal multi-purpose signaling tools. 812 84

Primary cultures of oligodendrocytes and astrocytes and purified cultures of Schwann cells were prepared respectively from forebrain and sciatic nerves of newborn rats. The effects of steroid hormones and growth factors on glial cell growth and on the production of myelin-specific proteins and lipids were investigated. Progesterone (P, 100 nM) decreased the proliferation of glial cells of the central nervous system. This inhibitory effect of P was abolished by the simultaneous administration of the antagonist RU486, thus suggesting a receptor-mediated action of the hormone. The expression of myelin-specific proteins, including the myelin basic protein (MBP) and the 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase), and of a myelin-specific lipid, galactocerebroside (Gal C), was also measured during cell differentiation under different hormonal conditions. The expression of MBP in oligodendrocytes was increased by P, and this effect was not blocked by RU486. The combined application of P and insulin promoted a synergistic stimulation of MBP expression. Insulin, by itself, also increased the number of MBP-positive oligodendrocytes in culture. The effects of P and insulin appeared to be selective as dexamethasone, dehydroepiandrosterone, pregnanolone and epidermal growth factor (EGF) had no effect. Only estradiol (E2, 500 nM) increased the number of MBP-immunoreactive cells, but in contrast to P, only a small synergism between E2 and insulin on MBP expression was observed. The expression of CNPase, another myelin-specific protein, was also increased by P and, here again, a synergy between P and insulin could be observed. In contrast, the expression of Gal C, a myelin-specific lipid, was not modified by P or other steroid hormones. Moreover, the increase in Gal C-positive cells observed in response to insulin alone was not further potentiated by P. Glial cells of the peripheral nervous system, namely Schwann cells, are also sensitive to steroid hormones. Schwann cells contain estrogen receptors, and E2 stimulates their proliferation in the presence of forskolin or dibutyryl cyclic AMP (dbcAMP). The mitogenic effect of E2 was abolished by the pure antiestrogen ICI-164,384. Insulin, at micromolar concentration, also stimulated Schwann cell growth when forskolin or dbcAMP were present in the culture medium. The mitogenic effect of insulin was mediated by insulin-like growth factor I (IGF-I) receptors. Indeed, at a physiological nanomolar concentration, IGF-I but not insulin or IGF-II, increased the proliferation of Schwann cells in synergy with forskolin. In addition, Schwann cells express receptors for IGF-I.
J Steroid Biochem Mol Biol 1994 Jan
PMID:Actions of steroid hormones- and growth factors on glial cells of the central and peripheral nervous system. 813

The mechanism of stimulation of DNA synthesis by microtubule-associated protein 2 (MAP2) was examined in the nuclear matrix isolated from Physarum polycephalum. Porcine brain MAP2 stimulated DNA synthesis by the matrix with exogenous templates, but not with endogenous templates. Kinetic analyses showed that MAP2 decreases the Km of the matrix for deoxyribonucleoside triphosphates. Comparison of the Km values of active- and latent-type DNA replication machineries of Physarum suggested a possible role for MAPs or MAP-like proteins in DNA replication.
Biochem Mol Biol Int 1993 Dec
PMID:Modulation of DNA synthesis by microtubule-associated protein 2 in the nuclear matrix isolated from Physarum polycephalum. 813 8

Accumulated evidence indicates that the adrenal cortex is able to regulate prolactin (PRL) secretion in rats. The aim of this study was to determine the participation of adrenal steroids on the regulation of PRL release in ovariectomized (OVX) and oestrogen-treated rats, by using mifepristone or a specific progesterone antiserum. Blood samples were obtained at 13:00 and 18:00 h 3 days after priming with oestradiol benzoate (OB). A significant increase in serum PRL at 13:00 and 18:00 h was induced by OB treatment. The administration of mifepristone to OVX and oestrogen-primed rats enhanced serum PRL increase at 13:00 h, without modifying the values at 18:00 h; while the administration of progesterone antiserum did not modify PRL levels, indicating that the effect of mifepristone on PRL secretion is due to its antiglucocorticoid action. Adrenalectomy induced a release of PRL at 13:00 h similar to that observed in the OVX and oestrogen-primed rats after mifepristone administration. Treatment with a low dose of progesterone (0.1 mg/rat) to OVX, adrenalectomized and oestrogen-primed rats did not modify the effect of adrenalectomy in serum PRL. Progesterone (2 mg/rat) given at 08:00 h to OVX and oestrogen-primed rats increased serum PRL 5 h later. Mifepristone treatment partially reverted the PRL increase induced by progesterone. These results suggest that after a previous sensitization of the pituitary by oestrogen, circulating glucocorticoids may exert a direct inhibitory effect on PRL release. This inhibition takes place at 13:00 h on day 3. On the other hand, the lack of effect of mifepristone or adrenalectomy on the PRL release at 18:00 h may also indicate that neither progesterone nor glucocorticoids modify PRL release induced by oestrogen at this time.
J Steroid Biochem Mol Biol 1994 Mar
PMID:Mifepristone treatment demonstrates the participation of adrenal glucocorticoids in the regulation of oestrogen-induced prolactin secretion in ovariectomized rats. 814 16

p42/Mitogen activated protein kinase (MAPK) and MAP Kinase Kinase (MAPKK) activities are constitutively elevated in v-raf transformed NIH3T3 cells, which correlates with increased tyrosine phosphorylation of p42mapk protein. These activities can be further enhanced to a moderate extent by treatment of raf-transformed cells with either serum, tetradecanoyl phorbol acetate (TPA), or aluminium fluoride. A similar activation of MAPK is observed in a cell line (M17raf) coexpressing a dominant inhibitory ras mutant (N-17 ras) along with v-raf. However, in this cell line, both the serum and TPA stimulated response of MAPK activity is reduced compared to similarly treated raf-transformed cells, while aluminium fluoride is equally potent in all the cell lines tested. These studies indicate that in addition to c-Raf-1, serine/threonine kinase, which is an upstream activator of MAPK, other c-ras dependent as well as c-ras independent pathways also can contribute to MAPK activation.
Cell Mol Biol Res 1993
PMID:Multiple pathways for activation of MAP kinases. 817 94

The intracellular free calcium concentration [Ca2+]i of sperm from 23 ejaculates was measured before and after cryopreservation using the fluorescent probe Fura-2. Spermatozoa were treated with 3.18 microM progesterone so that the regulation of [Ca2+]i in a dynamic situation could be studied. [Ca2+]i (nM) was 290 +/- 13 in fresh spermatozoa vs. 550 +/- 26 in cryopreserved samples (mean +/- S.E.M. P < 0.0001 paired t-test). Progesterone at a dose of 3.18 microM stimulated a large and rapid increase in [Ca2+]i to a peak value > 1 microM after 10-20 seconds. [Ca2+]i then declined to a slightly raised basal level over the next 30-40 seconds. This phenomenon occurred in all the fresh samples, but about half the frozen thawed samples failed to respond. The peak [Ca2+] attained by frozen samples which did respond after the addition of progesterone was similar to that observed with fresh sperm. The calcium channel blocker verapamil (200 microM) completely inhibited the transient rise in [Ca2+]i produced by progesterone, but 100 microM verapamil had only a partial effect. We conclude that (1) cryopreservation causes a substantial elevation of the [Ca2+]i in human spermatozoa and (2) damage to the plasma membrane during cryopreservation may result in the loss of the progesterone receptor. Both factors may contribute to the loss of fertility after cryopreservation.
Mol Reprod Dev 1994 Feb
PMID:Effects of cryopreservation on the intracellular calcium concentration of human spermatozoa and its response to progesterone. 817 8


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