Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Prolactin binding sites have been reported in a variety of tissues that are hormonally responsive to prolactin (PRL). A synergistic effect of PRL and androgens upon the secondary sexual structures of the male rat has been demonstrated. The present study was designed to: 1) determine if there are PRL binding sites in a membrane-rich particulate fraction of the rat ventral prostate: and 2) study the effect of changing the hormonal environment upon this specific PRL binding. The binding of lactoperoxidase iodinated ovine prolactin (I125-PRL) to rat prostatic membrane preparations was assayed by the method of Shiu and Friesen. Serum LH and PRL were measured by radioimmunoassay. The specific binding of I125-PRL that was observed in the prostatic membrane preparation of intact adult male rats was readily displaced by excess unlabelled ovine or rat PRL but not by rat LH or FSH. This binding was decreased by heating or trypsin treatment of the membrane preparation. Tissue specificity was demonstrated in that no specific binding was observed in membrane preparations of lung or spleen from these male rats. Prostatic membrane preparations from adult rats that were castrated for either 4 or 8 days showed a 90% decrease in specific I125-PRL binding while serum PRL values were not changed. Daily subcutaneous administration of testosterone propionate (2.0 mg/rat) to 4-day castrated adult rats resulted in I125-PRL binding comparable to that of intact rats. The data show that a reduction of endogenous androgens results in diminished I125-PRL binding in the ventral prostate of the rat.
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PMID:Prolactin binding in the rat ventral prostate. 81 36

The relationship between neuroendocrine regulation and the immune system has recently become the subject of intense investigations. The pituitary secretes both immunostimulatory (growth hormone and prolactin) and immunosuppressive (ACTH) hormones, and is thus involved in the control of immune functions. The present work was aimed at the study of the immunoregulatory properties of prolactin in selected in vitro and in vivo model situations. Prolactin was found to enhance recovery of the receptor for sheep red blood cells (in vitro). Compared with control cells, incubation with prolactin and/or prolactin containing sera significantly enhanced the capacity of trypsin treated lymphocytes from the peripheral blood of healthy volunteers to form E-rosettes. Chlorpromazine stimulated prolactin release in males, and lactation stimulated prolactin release in females raised the number of large granular lymphocytes in peripheral circulation. Sera containing elevated prolactin levels stimulated the metabolic activity of peripheral neutrophilic leukocytes. These results suggest that prolactin may stimulate selective functions of cellular immunity, and that it is involved in interactions between the nervous, the hormonal and the immune systems.
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PMID:Evidence for immunomodulatory properties of prolactin in selected in vitro and in vivo situations. 207

Prolactin receptors were purified from rat liver membranes by single-step immunoaffinity chromatography using a specific monoclonal antibody to the rat liver prolactin receptor. Scatchard analysis of 125I-human growth hormone binding to the purified receptor revealed two classes of specific binding sites with Ka = 18.5 x 10(9) and 1.2 x 10(9) M-1. Considering that both classes of binding sites are responsible for high affinity prolactin binding, the partially purified receptor preparation had a binding activity of 1.69 nmol/mg protein, representing 1000-fold purification over microsomal receptors with a recovery of 52%. From three separate purifications, 6 mg of partially purified prolactin receptor were obtained with a purity of approximately 4 to 6.5%. Thus, the use of monoclonal antibody for affinity chromatography resulted in a large improvement of prolactin receptor purification compared to previous hormone affinity chromatography (300-fold purification, 15% recovery). The purified receptor was run on preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis, and a homogeneous preparation of prolactin receptor was obtained by electroelution from gel slices corresponding to Mr 38,000-43,000. Immunoblot analysis using a radiolabeled monoclonal antibody revealed two separate but closely located bands of Mr 42,000 and 40,000 in microsomal, partially purified, and electroeluted preparations. The homogeneous receptor protein was extensively digested with L-1-tosylamido-2-phenylethyl chloromethyl ketone trypsin, and 10 internal amino acid sequences of the rat liver prolactin receptor were determined by gas-phase sequence analysis. Oligonucleotide probes were prepared against two of these internal sequences, and a prolactin receptor cDNA was isolated from a rat liver library using one of these probes (Boutin, J. M., Jolicoeur, C., Okamura, H., Gagnon, J., Edery, M., Shirota, M., Banville, D., Dusanter-Fourt, I., Djiane, J., and Kelly, P. A. (1988) Cell 53, 69-77). The amino acid sequence deduced from the cDNA reveals three potential sites of N-linked glycosylation, two of which were confirmed during protein sequencing. The prolactin receptor was characterized by affinity labeling with 125I-human growth hormone. Cross-linking of microsomes revealed a single band for the hormone-receptor complex with Mr 62,000. On the other hand, cross-linking of Triton X-100-solubilized or partially purified receptor with labeled hormone resulted in the appearance of two bands with Mr 62,000 and 102,000, suggesting the existence of a subunit structure of the prolactin receptor, or alternatively, the existence of two types of prolactin receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Purification and protein sequence analysis of rat liver prolactin receptor. 292 41

Glandular kallikrein is a major estrogen-induced protein of the rat anterior pituitary. A second kallikrein-like protease in the rat anterior pituitary (kallikrein A) is not affected by estrogens, nor is a third pituitary protease which cleaves a trypsin substrate but not kallikrein substrates. This study examined whether any of the pituitary proteases are regulated by dopaminergic mechanisms. Ovariectomized female rats were treated for 5-10 days with reserpine (a catecholamine depleting agent), haloperidol (a dopamine receptor blocker) or bromocriptine (a dopamine receptor agonist); some rats also received 1 or 2 micrograms estradiol benzoate every 48 h. Following activation of latent proteases with trypsin, anterior pituitary extracts were assayed for kallikrein activity before and after fractionation on DEAE-Sephadex to separate the two kallikrein-like proteases. Reserpine or haloperidol doubled glandular kallikrein levels in anterior pituitaries from estrogen-treated rats. Reserpine or haloperidol had little or no effect in the absence of estrogen (estrogen produced a 5- to 7-fold increase in glandular kallikrein in the absence of drug treatment). Bromocriptine markedly attenuated the ability of estrogen to induce glandular kallikrein. Further, bromocriptine blocked the ability of reserpine to increase glandular kallikrein levels, and haloperidol attenuated the effect of bromocriptine. Other anterior pituitary proteases were unaffected by either estrogen, haloperidol, reserpine or bromocriptine. The results demonstrate that the estrogen induction of glandular kallikrein in the rat anterior pituitary is modulated by inhibitory dopaminergic mechanisms. Prolactin is the only pituitary hormone which exhibits a similar profile of hormonal and neuroendocrine regulation; this suggests a possible link between glandular kallikrein and prolactin.
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PMID:Dopaminergic regulation of the estrogen-induced glandular kallikrein in the rat anterior pituitary. 302 15

Glandular kallikrein (a trypsin-like serine protease) is an estrogen-induced and dopamine-repressed protein in the rat anterior pituitary which appears to be associated with lactotrophs. This study examined glandular kallikrein levels in diethylstilbestrol (DES)-induced pituitary tumors in F344 rats and compared it to plasma and pituitary prolactin, and pituitary wet weight. Ovariectomized F344 rats were implanted with Silastic tubes containing 0 or 5 mg DES for 1, 3, 5, 7, or 9 weeks. Glandular kallikrein was measured by microenzymatic assay using D-valylleucylarginyl-p-nitroanilide following trypsin treatment of extracts to activate latent forms of glandular kallikrein. Prolactin was measured by radioimmunoassay. DES induced steady time-dependent increases in pituitary wet weight with 7- and 16-fold increases observed by 5 and 9 weeks, respectively. Growth rates averaged 11.4 mg/week during the first 5 weeks of DES exposure, and then increased to 23.2 mg/week between weeks 5 and 9. Glandular kallikrein total activity (nmol/min/pituitary) increased 130- and 240-fold after 3 and 5 weeks of DES exposure, respectively, and then abruptly plateaued. The specific activity (nmol/min/mg protein) of glandular kallikrein peaked at 3-5 weeks (36-fold increase compared to controls) and then declined as pituitary protein but not glandular kallikrein continued to increase. Total pituitary prolactin constantly rose during DES exposure with 12- and 26-fold increases after 5 and 9 weeks, respectively. Plasma prolactin levels also continuously rose during exposure to DES with 130- and 290-fold increases after 5 and 9 weeks, respectively. No major strain differences were found with regard to sensitivity to the acute effects of estrogen or dopaminergic stimulation on glandular kallikrein induction. DES-induced pituitary tumors in F344 rats are well known to arise via lactotroph proliferation, and the striking elevation in glandular kallikrein and prolactin during the early phases of tumor growth provide further support for a localization of glandular kallikrein in lactotrophs. However, the abrupt stabilization in glandular kallikrein levels by week 5 was unexpected and may signal a biochemical transformation of the tissue during tumor progression.
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PMID:Glandular kallikrein in estrogen-induced pituitary tumors: time course of induction and correlation with prolactin. 339 Aug 8

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

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

A 47-year-old woman was evaluated for congenital dwarfism, primary amenorrhoea due to hypogonadotrophic hypogonadism, severe hyperlipidaemia with pancreatitis, and overt diabetes mellitus associated with severe insulin resistance requiring 2.5-3 units of insulin per kilogram body weight. Chromosomal analysis with trypsin banding was normal and biochemical evaluation revealed low oestrogen levels, inappropriately low gonadotrophins, very low IGF-I concentrations and GH concentrations unresponsive to insulin or L-dopa administration. Prolactin, pituitary-adrenal and pituitary-thyroid axes were normal. Dynamic testing with GnRH and GHRH produced increases in FSH, LH and GH concentrations. A MRI of the brain revealed no discernible hypothalamic abnormalities and a small pituitary. The presence of congenital combined growth hormone and gonadotrophin deficiency on the basis of a suprapituitary defect suggests the existence of common or related pathways regulating GnRH and GHRH synthesis or secretion and may have contributed to the ultimate development of insulin resistance and hyperlipidaemia.
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PMID:Isolated combined growth hormone and gonadotrophin deficiency due to hypothalamic dysfunction, associated with insulin resistance. 755 20

The anterior pituitary (AP) gland secretes 6 different hormones. Prolactin (PRL) is secreted at a relatively high level without stimulation by the hypothalamus, while secretion of the others requires the action of stimulatory factors from the hypothalamus. In order to gain an insight into the mechanism underlying the different spontaneous release patterns of these hormones, we investigated their spontaneous release rate after pretreating rat anterior pituitary cells with trypsin. Rat AP cells were cultured on Cytodex microcarrier beads for 4 days and were then superfused with either control medium or medium containing trypsin (0.25%) for 5 min. The subsequent release rates of the AP hormones were monitored. The basal release of PRL was severely reduced to almost undetectable level and began to recover 120 min after the trypsin-pretreatment. Full recovery was attained over the next 100 min and was delayed by treatment with a protein synthesis inhibitor, cycloheximide (7 microM). In the trypsin-pretreated cells, basal release of PRL and growth hormone (GH) was severely reduced, while that of thyroid stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH) was enhanced and luteinizing hormone (LH) and follicle stimulating hormone (FSH) was not markedly affected by the treatment, suggesting that the suppression of PRL release was not caused by nonspecific damage to the cells. Since trypsin does not readily enter cells, the altered secretion of AP hormones seems to be the result of restricted digestion of the external components of the cells. On the bases of these observations, we predicted that the mechanism of spontaneous release of hormones involves trypsin sensitive proteins (TSMP) on the plasma membranes of the anterior pituitary cells.
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PMID:Alteration of basal release of anterior pituitary hormones by pretreatment of primary cultured cells with trypsin. 939 66

We have investigated a role for calcium-dependent cell-cell adhesion in the regulation of prolactin gene expression in rat pituitary GH(3) cells. Cells cultured in a calcium-free, serum-free medium (SFM) express low levels of prolactin and growth hormone mRNA. As expected, addition of 0.5 mM CaCl(2) to GH(3) cells in SFM produced a specific, severalfold increase in prolactin mRNA levels. CaCl(2) also promoted intercellular adhesion, during which cells assembled end-to-end in to cords. Prolactin mRNA increased after a delay of several hours. This latency period ranged from 4-12 h among different experiments, but always occurred after the onset of cell-cell adhesion. The voltage-sensitive calcium channel (VSCC) blocker, nitrendipine, inhibited the CaCl(2)-induced increase in prolactin mRNA without affecting cord formation. However, the VSCC agonist, BAY K-8644, was unable to induce prolactin gene expression prior to the onset of intercellular adhesion at 8 h, even though it produced a cellular response (tyrosine phosphorylation of a ca. 130-kDa protein) within 30 min. Blocking cell-cell adhesion inhibited the calcium-dependent induction of prolactin gene expression. Low levels (0.0025-0.02%) of trypsin blocked cell-cell adhesion and the prolactin mRNA induction by CaCl(2) without affecting the levels of other mRNAs or cell-matrix adhesion. Heparin also specifically blocked the induction of both cell-cell adhesion and prolactin gene expression. Based on these data, we propose a role for both VSCCs and calcium-dependent cell-cell adhesion in the induction of prolactin gene expression by extracellular CaCl(2).
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PMID:Role of cell-cell adhesion in the regulation of prolactin gene expression by extracellular CaCl(2). 2115 86


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