Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the major actions of prolactin in the mammary cell is to activate the expression of casein genes by enhancing the transcription rate of the genes. Anti-prolactin receptor antibodies can mimic prolactin action when added to mammary cells, suggesting that a relay is formed at the membrane level and transferred to the target genes. None of the classical hormone intracellular relays can account for the transfer of the prolactin message. The incubation of membranes from various tissues containing prolactin receptor with prolactin provokes the release of a factor which specifically accelerates the transcription of the beta-casein gene in isolated mammary nuclei. The factor is thermostable, inactivated by trypsin and is eluted from G-10 Sephadex as a molecule smaller than 1000 daltons. The action of the factor is prevented by phosphatase inhibitors. These results are strikingly reminiscent of those obtained with insulin which activates enzymes via a factor released from the membranes and which dephosphorylates the enzymes. The analogy between the action mechanism of prolactin and insulin is discussed.
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PMID:[Comparison of the mechanism of action of insulin and prolactin]. 630 40

Prolactin is a hormone involved in the control of many functions, from osmoregulation in fishes to lactation in mammals. For that reason, the control of its secretion by hypophysis is particularly complex. Multiple factors of hypothalamic origin (dopamine, GABA, VIP, etc . . .) and hormones (oestrogens, TRH, thyroxine, . . .) are involved in this control. Prolactin molecule contains about 200 aminoacids. It has three disulfide bridges, of which one, at the center of the molecule, is required for the lactogenic activity. The expression of prolactin gene is dependent upon oestrogens, TRH, Ca++ ion and cAMP which favour its transcription. In contrast, dopaminergics such as CB 154 lower the expression rate of this gene. Prolactin receptor is located essentially on the plasma and intracellular membranes of target cells. Its essential binding part has a molecular weight of about 40,000. In mammary gland and liver prolactin receptor is up-regulated following a slow process. It is also down-regulated following a rapid and reversible process. In mammary gland, prolactin controls the expression of milk protein genes by enhancing their transcription rate and also by increasing the stability and the translation rate of the mRNAs. The transfer of the prolactin information to genes takes place through a relay which is released from plasma membrane when the receptor is occupied by the hormone or by anti-prolactin receptor antibodies. This relay which seems to be a small peptide (less than 1000 daltons and inactivated by trypsin) acts directly and specifically on isolated mammary nuclei via a dephosphorylation of nuclear proteins.
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PMID:[Recent data on the mechanism of action of prolactin]. 631 Oct 73

Diethylstilbestrol (DES) treatment of weanling F344 female rats resulted in enlarged pituitary glands and diffuse pituitary prolactin (PRL) cell hyperplasia in all animals after 9 and 12 weeks of treatment. Serum PRL was significantly greater than in control rats (P less than 0.001). Immunohistochemical studies showed that most of the pituitary gland cells consisted of PRL cells. Ultrastructural studies showed increased numbers of PRL cells with hyperplasia of the rough endoplasmic reticulum and decreased numbers of secretory granules. There was a decrease in the relative number of growth hormone (GH) and other cell types in the anterior pituitary. Pituitary tumors and normal pituitary glands were dissociated with trypsin and maintained in culture for 3 weeks. The numbers of PRL and GH cells decreased with time in both groups, and there was an increase in the number of fibroblasts. Staining of the culture cells with neuron-specific enolase showed that the anterior pituitary cells were positive for this enzyme, while the fibroblastic cells were negative. When dissociated pituitary cells were cultured in the presence of 10(-9) M DES for 7 days, there was a 42% increase in the number of immunoreactive PRL cells. These results indicate that DES-treated rats provide an excellent model for study of the in vivo and in vitro regulation of pituitary hyperplasia and neoplasia.
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PMID:Estrogen-induced hyperplasia and neoplasia in the rat anterior pituitary gland. An immunohistochemical study. 663 50

We have demonstrated previously that many human cancer cell lines maintained in tissue culture possess specific cell surface receptors for human prolactin (HPRL) and human growth hormone (HGH). In the present studies, the biological response in vitro of one human breast cancer cell line, T-47D, to the two pituitary hormones was examined. T-47D cells, when grown on tissue culture dishes, display typical epithelioid characteristics; cells are flat and polygonal in shape and are very adhesive to the plastic substratum. Upon the addition of HPRL or HGH (10 to 1000 ng/ml), in the presence of hydrocortisone, insulin, and triiodothyronine, each at 1 microgram/ml, the T-47D cells became round and refractile. In addition, there was a dramatic reduction in the adhesiveness of the cells to the substratum; 80% of the hormone-treated cells were detached by trypsin (25 micrograms/ml) in 30 min at 37 degrees, as compared with 5% for cells not treated with hormones. These prolactin-induced changes could be abolished upon the addition of antiserum to prolactin. Neither HPRL nor the combination of hydrocortisone, insulin, and triiodothyronine alone was active, indicating a synergism between HPRL and hydrocortisone, insulin, and triiodothyronine. It was subsequently found that only hydrocortisone was required for the action of HPRL, and that human luteininzing hormone and ovine growth hormone were inactive, whereas ovine prolactin exerted a very weak effect. In addition, in the presence of hydrocortisone (or hydrocortisone, insulin, and triiodothyronine), HPRL (or HGH) retarded cell proliferation by 30%, whereas HPRL or hydrocortisone by itself had no effect on cell growth. Ultrastructural studies revealed that, accompanying cell rounding and reduced adhesion, HPRL and HGH increased the formation of intracytoplasmic lipid droplets in the T-47D cells. The increase in lipid synthesis was confirmed by the staining of cells with Oil Red O, and by monitoring the incorporation of [14C]acetate into lipid; HPRL stimulated lipid synthesis and accumulation by approximately 2-fold. Thus, receptor-positive human breast cancer cells are biologically responsive in vitro to HPRL and HGH.
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PMID:Alteration of cell shape, adhesion, and lipid accumulation in human breast cancer cells (T-47D) by human prolactin and growth hormone. 669 2

The expression of casein genes is under the control of several hormones of which the most important are prolactin, glucocorticoids and progesterone. In pseudopregnant or mid-pregnant rabbit having partially developped but inactive mammary gland, prolactin induces casein synthesis. The phenomenon is accompanied by an accumulation of casein mRNAs and by a stimulation of their translation. The accumulation of casein mRNAs results from an acceleration of the transcription of the corresponding genes and from a stabilization of the mRNAs. These prolactin effects are amplified by glucocorticoids which are not per se inducers and they are inhibited by progesterone. The essential action of prolactin and glucocorticoids can be obtained in cultured mammary explants and epithelial cells. This induction is accompanied by a transformation of the mammary cell in which are accumulated ribosomes and membranes involved in milk synthesis and exportation. This transformation is favoured by prolactin and inhibited by progesterone. Hence, the abundant milk secretion is triggered only after parturition when the predominence of progesterone is reversed in favour of prolactin. Prolactin incubated with mammary membranes promotes the formation of a factor capable of accelerating beta-casein gene transcription when added to isolated mammary nuclei. This factor is formed only by lactogen hormones and from prolactin receptor containing membranes. The information contained in the factor seems to be understood only by prolactin target genes. The generation of the factor can be provoked by anti-prolactin receptor antibodies and it is inhibited by tubulin binding drugs such as colchicine. The molecule exhibiting prolactin-like activity has a small molecular weight, it is thermostable and inactivated by trypsin. The stimulation of beta-casein gene transcription is abolished when the factor is incubated with nuclei in the presence of phosphatase inhibitors. These facts suggest that prolactin after its binding to its peripheral receptors triggers the release of a small peptide which migrates to nuclei where it activates the transcription of the prolactin target genes through a dephosphorylation of nuclear proteins. This small peptide is a good candidate to the prolactin intracellular relay.
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PMID:[Control of the expression of milk protein genes by prolactin, glucocorticoids and progesterone]. 676 97

There are many convincing arguments to accept the existence of inhibin. This hormone is produced inside the seminiferous tubules by the Sertoli cells in males and by the granulosa cells of the follicule in females. The biological, immunological and chemical characteristics of testicular and ovarian inhibin are identical so that it could be speculated the same molecule is secreted by both organs. This hormone is not a knownsteroid but is a protein substance. Thus, its biological activity is destroyed by trypsin and pepsin digestion and by heating at 60 degrees for 30 minutes. Furthermore, immunization with inhibin from rete testis fluid induces antibodies capable of neutralizing endogenous inhibin of adult male and female rats. This polypeptide hormone is not identical neither to ABP nor to a fragment of gonadotrophins. The molecular weight is not yet exactly defined and the possibility exists that two forms of inhibin are present in RTF: one of high (greater than 10,000 Daltons) and the other of low molecular weight. The high M.W. species could be a polymer or alternatively the combination of native inhibin and a carrier substance or unique precursor molecule. Inhibin preparations selectively depress the synthesis and the release of FSH in pituitary cell culture. The threshold dose to affect the LH production is higher than that active on FSH secretion. Furthermore, they reduce LH-RH content of hypothalamus maintained in organ culture. In animals, inhibin induced effects are depending on both hypothalamus and pituitary actions according to the functions of these two structures. In that sense, apparently contradictory results are obtained in short and long term castrated animals. Inhibin does not modify TSH, GH and prolactin in vivo and in vitro. This substance displays an inhibition on the synthesis of DNA in the testis of pubertal male rats and depresses the maturation of follicle in female.
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PMID:[Inhibin: new gonadal hormone (author's transl)]. 677 85

A purified basic protein from bull seminal plasma having inhibin activity was labeled with 125I and tested for binding with ovine pituitary membrane fractions. The bound radioactivity could be eluted under acidic conditions and shown to rebind to fresh pituitary membranes. The properties of the eluted labeled inhibin were similar to the unlabeled fraction. The eluted labeled inhibin exhibited specific binding to the membranes, which was displaceable in a dose-dependent manner by an unlabeled active fraction. Only those fractions in the purification scheme which had inhibin activity also competed for the binding. A bovine follicular fluid fraction with molecular weight greater than 10 000 and inhibin activity also displaced the bound radioactivity from the membranes. Other purified hormones such as ovine FSH, LH or their subunits, prolactin or bovine serum albumin, dialyzed serum or unrelated basic macromolecules such as lysozyme, polylysine, histones, had no influence on the binding of labeled inhibin to ovine pituitary membranes. Synthetic LH-RH also failed to displace the labeled inhibin from the membranes. The binding was sensitive to heat and trypsin treatments. The data are consistent with the direct action of inhibin on the pituitary and demonstrate the existence of binding sites for the active fraction in this target.
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PMID:Binding of an inhibin-like protein from bull seminal plasma to ovine pituitary membranes. 678 37

Two possibilities of an inhibition of gastric acid secretion are compared in regard to effectiveness and side effects. Combined i.v. bolus injection of 0.3 mg/kg cimetidine caused almost complete inhibition of peptone-stimulated acid secretion in normal volunteers and duodenal ulcer patients-radomized and double blind investigated-to the same extent as high dose secretin (3 CU/kg/h i.v. infusion) in normal volunteers. Postprandial gastrin was unchanged by combined drug application, but was suppressed by secretin. Temporary blurred vision, dry mouth, and signifiant increase of serum prolactin were side effects of the drug combination, whereas secretin caused dose-dependent diarrhoea, increaded diuresis and elecvation of serum lipase, trypsin, and sodium. Inhibition of acid secretion by combination of the antimuscarinic drug pirenzepine with the H2-receptor blocking substances cimetidine was almost complete, i.e. more effective than the combination of classic anticholinergics with H2-blockers tested so far. Inhibition of acid secretion by secretin was dose-dependent; the dosage clinically applied so far (10 CU/kg s.c. and 0.5 CU/kg/h i.v.) had the smallest effect. In spite of first favourable results with secretin in bleeding mucosal lesions, the observed side effects cast doubt on its broad clinical applicability. A controlled clinical trial of the combination of cimetidine plus pirenzepine as prophylaxis of bleeding from mucosal lesions in risk patients seems to be indicated.
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PMID:[Effectiveness of cimetidine, pirenzepine and synthetic secretin on stimulated gastric acid secretion]. 689 78

Extracts of frozen human pituitaries were mitogenic in a fetal rabbit chondrocyte bioassay. In the presence of 10% fetal bovine serum, a 10-fold increase in chondrocyte cell number was observed upon addition of the pituitary factor to the culture medium. After gel filtration, the chondrocyte growth factor eluted with proteins of approximately 40,000 molecular weight. These fractions were pooled and purified further upon ion exchange chromatography using DEAE-cellulose. The most active fraction stimulated cell proliferation in a dose-dependent manner down to 10 ng/ml. The chondrocyte growth factor was trypsin- and heat-sensitive (100 degrees C, 10-15 min). Its isoelectric point (pI 7.9) was different from bovine brain and pituitary fibroblast growth factor (pI 4.8-5.8 and pI 9.5, respectively. Unlike the somatomedins and epidermal growth factor, it was acid-labile. Preparations of human growth hormone, prolactin, luteinizing hormone, and follicle-stimulating hormone, prolactin, luteinizing hormone, and follicle-stimulating hormone, as well as vasopressin and oxytocin, were inactive in the bioassay, demonstrating that the human pituitary contains a chondrocyte growth factor which appears to be distinct from these anterior and posterior pituitary hormones.
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PMID:Chondrocyte growth factor from the human pituitary gland. 689 56

The protein hormone prolactin was isolated from sea whale hypophysis and its amino acid sequence was partially characterized. The hormone was hydrolyzed by BrCN and trypsin, the products of hydrolysis were separated and purified by gel filtration on Sephadex G-50, G-100 and G-25, by ion-exchange chromatography on CM-cellulose and on Dowex 50 x 8 and by partition paper chromatography. The structure of the obtained peptides was determined by the Edman method and by carboxypeptidase A hydrolysis. The partial amino acid sequence of sea whale prolactin making up to 75% of the hormone molecule was established.
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PMID:[Isolation and partial characterization of the amino acid sequence of sea whale prolactin]. 708 86


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