Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of certain synthetic and endogenous steroids to modulate neuronal responses to gamma-aminobutyric acid (GABA) is well documented, but little is known of the effect of steroids on glycine responses. We show here that in voltage-clamped neurons progesterone (10-100 microM) itself enhances GABA-induced chloride currents but, surprisingly, antagonizes those induced by glycine. Some, but not all, progesterone metabolites also display these effects. The effects of progesterone on GABA and glycine responses are dose dependent, with EC50 values of 26 and 16 microM and maxima of +156 and -60%, respectively. Progesterone and its reduced metabolite 5 alpha-pregnan-3 alpha-ol-20-one potentiate GABA responses by acting through a common site. The site through which progesterone acts to inhibit glycine responses is distinct from the strychnine and glycine binding sites. These results not only provide an important distinction between chloride-mediated GABA and glycine responses but also suggest that endogenous progesterone or its metabolites may differentially modulate the inhibitory actions of these two neurotransmitters.
Mol Pharmacol 1990 May
PMID:Inverse modulation of gamma-aminobutyric acid- and glycine-induced currents by progesterone. 233 42

The effects of oestradiol and progesterone on LH-subunit mRNA levels were investigated in ovariectomized rats. Four weeks after ovariectomy, rats were implanted with silicone elastomer capsules containing oestradiol and/or injected daily with progesterone in oil (5 mg/rat) for 8 days. The levels of pituitary mRNA encoding alpha and LH-beta were determined using direct hybridization with specific [32P]cDNA probes. After oestradiol implantation in ovariectomized rats, both alpha and LH-beta mRNA decreased with time, with maximum inhibition after 6-8 days of treatment. Progesterone injected alone did not show any effect on alpha and LH-beta mRNA. Cytosolic progesterone receptors, determined using [3H]methyl-17 alpha-progesterone as ligand, were undetectable in control ovariectomized rats. In contrast, 2 days after oestradiol implantation, the number of receptors increased to 287.5 +/- 35.4 (S.E.M.) fmol/pituitary and reached a plateau of 400 +/- 21.8 fmol/pituitary after 4 days. The effects of progesterone were therefore examined by first implanting ovariectomized rats with oestradiol to induce progesterone receptors and then injecting progesterone daily for a further period of 6 days. As a result of this treatment, progesterone induced a decrease in the pituitary gland contents of both alpha and LH-beta mRNAs, and LH release was significantly greater than that observed in the group receiving oestradiol alone. Moreover, the mRNA levels in the animals treated with oestradiol plus progesterone were lower after 8 days of treatment than those observed in ovariectomized rats treated with a tenfold higher dose of oestradiol alone.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Endocrinol 1990 Apr
PMID:Synergistic effects of progesterone and oestradiol on rat LH subunit mRNA. 234 89

Prostatic steroid-binding protein (PBP) is the most abundant protein synthesized in the rat ventral prostate. The protein is under strict androgenic control and is made of two subunits containing the polypeptides C1, C2 and C3. Using an 35S-labelled cDNA probe, we have used quantitative in-situ hybridization to assess the regulation of polypeptide C1 mRNA levels by sex steroids in the adult male rat. Densitometric quantification of autoradiographic hybridization signals revealed that a significant decrease in C1 mRNA levels could be detected 5 h after castration. Levels of C1 mRNA decreased by 50% 2.5 days after castration, while undetectable levels were reached within 7 days. Administration of the potent androgen 5 alpha-dihydrotestosterone to castrated rats caused a progressive increase in C1 mRNA levels which became significant 5 h after the first injection, while prolonged treatment, for 3 and 7 days, caused 50 and 100% reversals respectively of the effect of castration on C1 mRNA levels. Similar results were obtained by dot-blot hybridization using the same 32P-labelled cDNA probe, thus confirming the specificity and quantification achieved by in-situ hybridization. Administration of oestradiol-17 beta to orchiectomized adult rats for 14 days had no effect on steady-state C1 mRNA levels. Progesterone, on the other hand, at the dose used (2 mg twice daily) caused a marked increase in C1 mRNA levels, measured by in-situ hybridization, which was completely reversed by concomitant administration of the pure antiandrogen flutamide. The present data clearly demonstrate that the expression of PBP C1 peptide mRNA is under strict androgenic control and is a very sensitive and specific parameter of androgenic activity. They also indicate that quantitative in-situ hybridization is a powerful, sensitive and most efficient tool to study the regulation of gene expression while, in addition, providing precise information about the site of mRNA localization as well as information about the histology of the tissue, particularly the heterogeneous nature of the acinar response to androgenic stimulation and deprivation.
J Mol Endocrinol 1988 Nov
PMID:Effects of sex steroids on regulation of the levels of C1 peptide of rat prostatic steroid-binding protein mRNA evaluated by in-situ hybridization. 247 28

Antibodies against the N-terminal domain of the human androgen receptor (hAR) were prepared by two different approaches. Firstly, rabbits were immunized with a beta-galactosidase-hAR (amino acids (aa) 174-353) fusion protein. Secondly, two synthetic peptides corresponding to potentially antigenic sites located within this fragment (aa 201-222 and 301-320) were used as immunogens. The obtained antisera contained high titer anti-hAR antibodies as was established with several independent methods (e.g. sucrose gradient centrifugation, immunoprecipitation, Western blotting). The two anti-peptide antisera specifically stained nuclei of glandular epithelial cells in frozen sections of human prostate tissue. Progesterone, estradiol and glucocorticoid receptors were not immunoprecipitated with these antisera. The specific hAR antibodies provide new tools for the characterization of this steroid receptor as well as for diagnostic purposes in pathology of the human prostate and androgen resistance.
Mol Cell Endocrinol 1989 Nov
PMID:Characterization of polyclonal antibodies against the N-terminal domain of the human androgen receptor. 248 9

The present experiments examined the effects of progesterone on adrenergic receptor coupling to adenylate cyclase in hypothalamic and preoptic area slices by monitoring norepinephrine (NE)-stimulated increases in cAMP accumulation. Progesterone treatment of estrogen-primed rats decreased NE-induced slice cAMP accumulation. The reduced cAMP response was estrogen-dependent since it was not demonstrable in slices from rats exposed to progesterone without prior estrogen priming. Neither generalized increases in phosphodiesterase activity nor decreases in the catalytic activity of adenylate cyclase could account for the reduced ability of NE to stimulate cAMP accumulation in hypothalamic slices. Moreover, the cAMP response to two other activators of adenylate cyclase, adenosine and vasoactive intestinal peptide, was not decreased in slices from rats treated with estrogen plus progesterone. Selective adrenergic agonists and antagonists were employed to determine which adrenergic receptors mediate cAMP accumulation in progesterone-exposed slices. Slice cAMP levels were elevated by the beta receptor agonist isoproterenol but not by alpha 1 (phenylephrine) or alpha 2 (clonidine) agonists. However, clonidine potentiated the effect of isoproterenol on slice cAMP formation whereas phenylephrine did not. Likewise, NE-stimulated cAMP accumulation was completely antagonized only by a combination of both beta (propranolol) and alpha 2 (yohimbine) antagonists. The data suggest that in slices from estrogen plus progesterone-treated rats, alpha 2 receptors contribute significantly to NE stimulation of cAMP accumulation. The overall depression of the cAMP response to NE in progesterone-exposed slices may involve a decrease of alpha 1 receptor facilitation of cAMP synthesis.
Brain Res Mol Brain Res 1989 Mar
PMID:Progesterone depression of norepinephrine-stimulated cAMP accumulation in hypothalamic slices. 254 2

The aim of this work was to determine whether dexamethasone (Dex), a synthetic glucocorticoid, counteracts the stimulatory effects of estradiol (E2) on MCF-7 cells. We have shown that Dex inhibits in a dose-dependent fashion the estradiol-stimulated cell proliferation. This inhibition (ID50 congruent to 5-10 nM), which is complete at 100 nM Dex, is prevented by the antiglucocorticoid RU 486 and is clearly different from that found with trans-4-OH-tamoxifen because the inhibition due to a fixed concentration of Dex is not abolished by a high concentration of estradiol. This inhibitory effect displays some degree of specificity. Progesterone and the progestins R 5020 and ORG 2058 are without effect and Dex does not alter the triiodo-L-thyronine-stimulated cell growth. To characterize further the antiestrogenic action of Dex, the effects of this drug on specific responses to estradiol were studied. (1) Among the positive responses to estradiol two are prevented by Dex (the increase of concentration of progestin receptors and that of immunoreactive insulin-like growth factor I, IR-IGF-I, in conditioned medium) and two are insensitive to Dex (the enhancement of the secretion of 52,000 and 160,000 Mr proteins). (2) A negative response to estradiol (the down-regulation of estrogen receptor) is not prevented but rather accentuated by Dex. Thus, Dex counteracts the stimulatory effects of estradiol on the proliferation of MCF-7 cell variants characterized by progestin insensitivity. This non-classical antiestrogenic effect could be due in part to the attenuation of the E2-induced IR-IGF-I secretion and, less probably, to the accentuation of the down-regulation of E2 receptors. It could account for certain therapeutic and/or side effects of glucocorticoids on estrogen target cells.
Mol Cell Endocrinol 1989 Oct
PMID:Non-classical antiestrogenic actions of dexamethasone in variant MCF-7 human breast cancer cells in culture. 261 31

We describe two apical surface integral membrane glycoproteins which appear to be differentiation markers of the human pulmonary alveolar type 2 cell which has as a major function the production of pulmonary surfactant. These membrane glycoproteins bind the lectin, Maclura pomifera agglutinin and can be found in detergent extract of whole lungs, lung membranes and isolated type 2 cells. One of the MPA binding glycoproteins (MPA-gp330) has an apparent molecular weight of 330 kD and is analogous to a similar membrane glycoprotein found in rat and rabbit type 2 cells. The other glycoprotein (MPA-gp350/390) is an antigen found on the surface of many human cancer cells. In studies of human fetal lung tissue we found that MPA-gp350/390 is expressed before known surfactant functions of the type 2 cell while MPA-gp330 appears later. Neither glycoprotein is influenced by glucocorticoids yet surfactant synthesis is hormone-dependent. These studies demonstrate that pulmonary type 2 cell differentiation is a more complex process than previously appreciated and that differentiation markers are expressed in a discoordinate fashion and regulated by different factors.
J Mol Cell Cardiol 1989 Feb
PMID:Alveolar cell differentiation markers in human lungs. 273 26

Granulosa cells from immature female rats, pretreated with pregnant mare's serum gonadotropin, were cultured with microcarrier beads for 24 h, and superfused with culture medium. Progesterone was transiently released following a 10-min pulse of FSH (100 ng/ml), and there was a self-priming effect of FSH. 10-min pulses of 8-bromo-adenosine 3',5'-cyclic monophosphate (8Br-cAMP) (1 mg/ml) mimicked the effects of follicle-stimulating hormone (FSH). Continuous superfusion with FSH induced biphasic secretion of progesterone, which was composed of a parabolic (the first) and a plateau (the second) phase. By contrast, the pattern of secretion induced by continuous superfusion with 8Br-cAMP was monophasic. FSH-stimulated secretion of progesterone was rapidly inhibited by the addition of 10 microM cycloheximide (CX), but secretion recovered upon removal of this inhibitor. In the second phase, the recovery of secretion was accompanied by an overshoot of the plateau value. The present results suggest that: (1) the generation of the time-related biphasic pattern of secretion cannot be interpreted by cAMP alone; (2) FSH stimulates the secretion of progesterone by a mechanism that involves newly synthesized protein.
Mol Cell Endocrinol 1988 Oct
PMID:Dynamic response to follicle-stimulating hormone of secretion of progesterone by superfused rat ovarian granulosa cells. 284 83

We describe the isolation of a cloned cDNA from a cDNA library of oviduct of estrogen-treated adult Xenopus. Although the protein encoded by this cDNA is not known, it is designated as FOSP-1 (frog oviduct-specific protein-1). A partial restriction map of FOSP-1 cDNA, which is 1.5 kb in size, is presented. Northern hybridization analysis showed that FOSP-1 cDNA codes for a single species of mRNA of 2.6 kb which is exclusively expressed in Xenopus oviduct. Southern blot analysis showed that the gene was present in only one or two copies. Sequencing of partial FOSP-1 cDNA did not reveal homology with any protein in the sequence data bank. Measurement of steady-state levels of FOSP-1 mRNA in primary cultures of Xenopus oviduct cells by a technique of quantitative slot-blot analysis showed that both 17 beta and 17 alpha stereoisomers of estradiol caused a rapid 5-fold enhancement of accumulation of the mRNA with maximum values obtained at 5 X 10(-8) M estrogen. Progesterone caused only a small increase in FOSP-1 mRNA concentration. This hormone-specific induction of mRNA makes FOSP-1 a valuable candidate for exploring tissue specificity of regulation by estrogen of gene expression.
Mol Cell Endocrinol 1988 Oct
PMID:FOSP-1 (frog oviduct-specific protein-1) gene: cloning of cDNA and induction by estrogen in primary cultures of Xenopus oviduct cells. 284 84

Cultured human endometrial stromal cells were found to release placental protein 5 (PP5), a glycoprotein with properties of a serine protease inhibitor. Progesterone had no effect on PP5 release, but cholera toxin and 12-O-tetradecanoylphorbol 13-acetate stimulated PP5 release in a time- and concentration-dependent fashion. Prostaglandin E2 (PGE2) caused a parallel increase in cAMP and PP5 release in a time- and concentration-dependent fashion. The lowest PGE2 concentration which increased cAMP and PP5 release was 1 X 10(-9) M. Maximal increase in cAMP (42-fold) and PP5 (25-fold) release was obtained by 10(-5) M PGE2. Stimulation of cAMP by PGE2 was detectable at 15 min and was followed by an increased PP5 release at 24 h. The concentrations of prostaglandin F2 alpha (PGF2 alpha) which stimulated cAMP and PP5 release were pharmacological suggesting that this effect is nonspecific. The results indicate that the activation of cAMP- and protein kinase C-dependent pathways in endometrial stromal cells increases the production of PP5. PGE2 could be one of the physiological ligands employing the cAMP-dependent pathway in endometrial stromal cells.
Mol Cell Endocrinol 1988 Dec
PMID:Regulation of the production of placental protein 5 by human endometrial stromal cells; the role of prostaglandins E2 and F2 alpha. 285 Sep 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>