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 enhanced phosphorylations via cAMP, Ca2+ mobilization, and diacyl glycerol formation via the activation of the respective kinases is now classical. The decreased phosphorylation via inhibition of adenylate cyclase via the alpha adrenergic receptor is also becoming understood. What the insulin studies on the control of glycogen synthesis have taught us is that the rate limiting enzyme glycogen synthase is regulated by multiple covalent phosphorylation in an elegant but complex manner. The overall pattern of dephosphorylation is influenced by effecting both phosphatase and kinase activities in a set of interrelated mechanisms. In the presence of glucose, in muscle, fat, and liver under physiological conditions G-6-P acts as a signal to stimulate the phosphatase. An additional stimulation could occur via a novel insulin phosphatase stimulatory mediator. The phosphatase is also stimulated by at least three covalent mechanisms involving altered phosphorylation state. In one there is a decreased phosphorylation of the phosphatase inhibitor 1 potentially related to decreased cAMP-dependent protein kinase activity. In the second, there is decreased phosphorylation of the deinhibitor also potentially related to decreased cAMP-dependent protein kinase phosphorylation. In the third, an increased activity of casein kinase 2 could activate the ATP-Mg dependent phosphatase by an increased phosphorylation of phosphatase inhibitor 2 (modulatory subunit). In the liver, allosteric control of the phosphatase by G-6-P and nucleotides is of great importance. Insulin also stimulates the phosphatase in long-term experiments via increased protein synthesis. It is clear that future work will be required to determine which species of the various classes of phosphatases are regulated in short-term and long-term regulation by insulin. In terms of kinases, the effects of insulin to inactivate and desensitize the cAMP-dependent protein kinase are established. The molecular mechanisms of this effect remain to be worked out. The enhanced activity of MAP and S-6 kinase would appear to be part of a cascade of reactions perhaps originating in the autophosphorylation and activation of the insulin receptor tyrosine kinase. The mechanism of the short-term activation of casein kinase 2 remains to be elucidated. A cAMP-dependent protein kinase inhibitory mediator, which also inhibits adenylate cyclase is an important element in the regulation of kinase and adenylate cyclase activity by insulin. Its physiological significance must be established in the future, in terms of its control of glycogen synthase activation by insulin. Clearly this kinase inhibitor as well as the phosphatase stimulator are potential regulators of glycogen synthase activity by insulin.
Adv Enzymol Relat Areas Mol Biol 1990
PMID:Insulin and the stimulation of glycogen synthesis. The road from glycogen structure to glycogen synthase to cyclic AMP-dependent protein kinase to insulin mediators. 215 10

Progesterone has been shown to decrease occupied pituitary and uterine nuclear estradiol receptor (E2R) binding in mature and immature estrogen-primed rats. Progesterone has also been shown to stimulate pituitary but not uterine 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) in the rat. The conversion of estradiol to its less active metabolite estrone by 17 beta-HSD and activation of phosphatase are among mechanisms considered to be involved in the reduction of E2R. To determine if 17 beta-HSD stimulation was a mechanism by which progesterone induced nuclear E2R decrease, the synthetic estrogen ethinylestradiol, which is not oxidized by 17 beta-HSD, was used instead of estradiol to prime adult ovariectomized rats. When ethinylestradiol-primed rats received 0.8, 2.0 or 4.0 mg/kg body wt of progesterone 2 h before sacrifice, the total and occupied nuclear E2R accumulation in the anterior pituitary by a subsequent ethinylestradiol injection 1 h later did not show any decrease. This response was different from that observed previously in estradiol-primed animals in which progesterone showed a multiphasic decrease of occupied form of nuclear E2R. However, in the uterus of ethinylestradiol-primed rats, a partial decrease of total and occupied nuclear E2R accumulation was observed in the presence of the three doses of progesterone used. The decrease of uterine nuclear E2R with the three progesterone doses was different from the dose-dependent effect of progesterone observed in the uterus of estradiol-primed rats. Affinity constants of the interaction between [3H]estradiol and the nuclear E2R were similar among groups treated with ethinylestradiol, estradiol and progesterone. These results demonstrate the involvement of 17 beta-HSD in the reduction of anterior pituitary gland E2R by progesterone in the estradiol-treated animals. Furthermore, the mechanism of decrease of E2R by progesterone in the uterus appears to be different from the pituitary gland.
J Steroid Biochem Mol Biol 1990 Sep
PMID:Role of 17 beta-hydroxysteroid dehydrogenase in the modulation of nuclear estradiol receptor binding by progesterone in the rat anterior pituitary gland and the uterus. 217 25

In adults, the alveolar epithelium is composed of types I and II cells which differ structurally and functionally although they appear to belong to the same cell lineage. Using cell-specific markers (type I cells, monoclonal antibody; type II cells, Maclura pomifera lectin [MPA]), we have determined when and in what pattern their binding sites occur during development of the fetal rat lung. Rather than first appearing on days 19 to 20, when morphogenesis of type I cells occurs and lamellar bodies provide positive identification of type II cells, the markers appeared on day 15 (for type I cell marker) and day 16 (for type II cell marker). The type I cell marker was widespread by day 17 and was sufficiently abundant to be detected on a Western blot. MPA binding appeared more gradually and was often found on isolated cells. On serial sections of day 20 lung, the markers appeared to be localized to the same cells. The early appearance of cell-specific markers suggests an early onset of the developmental program that leads to full differentiation of types I and II cells. Co-expression of both cell-specific markers suggest that fetal cell lineage may differ from the scheme proposed by others that type II cells serve as type I cell precursors during development.
Am J Respir Cell Mol Biol 1990 Jun
PMID:Expression of cell-specific markers for alveolar epithelium in fetal rat lung. 218 57

Oestrogen and progesterone receptors were studied in the non-pregnant state, in early pregnancy and at term using monoclonal antibody enzyme immunoassays. Receptors for both steroids were found in tissues from non-pregnant patients and patients in early pregnancy. At term oestrogen receptors were undetectable in all tissues studied. Progesterone receptors were undetectable in chorion, amnion and placenta at term, while present in extremely low concentrations in decidua and myometrium.
J Steroid Biochem Mol Biol 1990 Nov 30
PMID:Enzyme immunoassay of oestrogen and progesterone receptors in uterine and intrauterine tissue during human pregnancy and labour. 227 34

To understand the mechanism of progesterone inhibition of the sodium influx in the toad skin, the effects of the hormone on the active sodium transport and oxidative metabolism of the transporting cells were examined. A direct relationship was observed between the initial value of the short circuit current and the sensitivity of a given skin toad preparation to progesterone. Progesterone had a higher effect on the sodium potential than on any other parameter of an equivalent electrical circuit of toad skin. Direct measurement of oxygen consumption indicated that progesterone can act as a blocking agent of the respiratory chain of the sodium transporting cells of toad skin.
Cell Mol Biol 1990
PMID:The action of progesterone on sodium transport of isolated toad skin. Further evidences of a metabolic action. 227 63

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


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