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:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gonadotropin binding and stimulation of cyclic adenosine 3':5'-monophosphate (cyclic AMP) formation and testosterone synthesis were studied in collagenase-dispersed interstitial cells from the adult rat testis. Binding of 125I-human chorionic gonadotropin (hCG) by isolated Leydig cells was of high affinity (Ka = 10(10) M-1) and low capacity, equivalent to approximately 6000 sites/cell. The binding data were consistent with the presence of a single order of receptors, with no interaction between binding sites. Stimulation of testosterone synthesis by increasing concentrations of hCG was completely dissociated from changes in cyclic AMP formation, and maximum activation of steroidogenesis was induced by hCG concentrations which had no effect upon cyclic AMP production. Kinetic analysis of gonadotropin-induced responses in dispersed Leydig cells also showed a marked dissociation between steroidogenesis and cyclic nucleotide formation. Low concentrations of hCG caused maximum stimulation of testosterone production which was not accompanied by a rise in cyclic AMP formation at any time after addition of gonadotropin. Higher concentrations of hCG caused marked elevations of cyclic AMP at progressively earlier time intervals, but did not alter the 20 to 30 min lag period required for induction of testosterone synthesis. These observations indicated that occupancy of gonadotropin receptors occurs over a much wider range of hCG concentration than that required for maximum steroidogenesis.
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PMID:Gonadotropin binding and stimulation of cyclic adenosine 3':5'-monophosphate and testosterone production in isolated Leydig cells. 17 Dec 67

Gonadotropic hormones are required for the induction and maintenance of tumors arising in ovaries that have been transplanted to the spleens of gonadectomized mice. The characteristics of gonadotropin receptors for human chorionic gonadotropin (HCG)-luteinizing hormone on cells from these tumors of varying size, age, and morphology have been determined. The specific binding of 125I-labeled HCG to cells obtained by collagenase digestion, 15 to 65 weeks postimplantation from granulosa cell or luteinized cell, or mixed granulosa-luteal tumors was analyzed by Scatchard plot. Neither the size, weight, duration of implantation, nor histological morphology affected the receptor-binding affinity [equilibrium dissociation constant (Kd), 6 X 10(-10) M], and, presumably, the receptor is qualitatively similar. In contrast, the number of HCG receptors per cell increased 17-fold and was related to the degree of morphological luteinization of the tumor. HCG-sensitive adenyl cyclase was also demonstrated and compared to HCG binding in a highly luteinized tumor.
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PMID:Gonadotropin receptors in experimentally induced ovarian tumors in mice. 19 83

Progesterone production in vitro, in the presence and absence of exogenous gonadotropin, was examined in suspensions of luteal cells, isolated by collagenase digestion of rhesus monkeys corpus luteum at various stages of the menstrual cycle. Cells isolated during mid-luteal phase (days 15-19) of the cycle secreted progesterone for up to 6 h in vitro. Mid-luteal phase cells were responsive to physiologic concentrations of human chorionic gonadotropin (hCG), with progesterone production significantly (P less than 0.05) enhanced by as little as 0.1 ng hCG/ml. Maximal stimulation was obtained with 100 ng hCG/ml. Both macaque chorionic gonadotropin (mCG) and human luteinizing hormone (hLH) significantly (P less than 0.01) increased progesterone production, while human follicle stimulating hormone (hFSH) did not. Under control conditions, in the presence of nutrient medium alone (no exogenous gonadotropin), the progesterone synthetic activity of mid-luteal phase cells was significantly (P less than 0.01) greater than that of cells from late luteal phase (days 22-28) of the cycle. Moreover, progesterone production by mid-luteal phase cells was consistently stimulated (P less than 0.01) by the presence of 100 ng hCG/ml, whereas late luteal phase cells were less sensitive or unresponsive to exogenous gonadotropin. The progesterone synthetic activity of luteal cells in vitro correlated positively with both the wet weight of the excised corpus luteum (r = 0.82, P less than 0.01) and the peripheral serum progesterone concentration immediately preceding luteectomy (r = 0.66, P less than 0.01). These findings suggest that freshly isolated luteal cells reflect the functional capability of the corpus luteum in vivo. It is apparent that the age of the rhesus monkey corpus luteum of the non-fertile menstrual cycle is an important factor governing luteal cell progesterone synthetic capability and luteal cell responsiveness to gonadotropin in vitro.
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PMID:Gonadotropin-sensitive progesterone production by rhesus monkey luteal cells in vitro: a function of age of the corpus luteum during the menstrual cycle. 40 32

Corpus luteum function in the cycling and the pregnant rhesus monkey (Macaca mulatta) was evaluated through short term in vitro studies of progesterone production by suspensions of collagenase-dispersed luteal cells in the presence and absence of exogenous gonadotropin (human chorionic gonadotropin, HCG). Cells from mid-luteal phase of the menstrual cycle secreted progesterone, as measured by accumulation of this hormone in the incubation medium, and responded to the addition of 100 ng HCG/ml with a marked increase in progesterone secretion significantly above basal level (63.7 +/- 13.1 versus 24.7 +/- 5.5 ng progesterone/ml/5 x 10(4) cells/3 hr, X +/- S.E., n =6 ; p less than 0.05). However, luteal cells from early pregnancy (23-26 days after fertilization) secreted siginificantly less progesterone than cells of the non-fertile menstrual cycle (3.6 +/- 2.4 versus 24.7 +/- 5.5 ng/ml/5 x 10(4) cells/3 hr, n =3 ; p less than 0.05) and did not respond to HCG with enhanced secretion. By mid-pregnancy (108-118 days gestation ) luteal cells exhibited partially renewed function, and near the time of parturition (163-166 days gestation) basal and HCG-stimulated progesterone secretion (30.2 +/- 5.6 and 63.0 +/- 13.0 ng/ml/5 x 10(4) cells/3 hr, respectively; n = 3) was equivalent to that of cells from the luteal phase of the non-fertile menstrual cycle. The data suggest that following a period around the fourth week of gestation, when steroidogenic activity is markedly diminished, the corpus luteum of pregnancy progressively reacquires its functional capacity and at term exhibits gonadotropin-sensitive steroidogenesis similar to that the corpus luteum of the menstrual cycle.
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PMID:In vitro evaluation of corpus luteum function of cycling and pregnant rhesus monkeys: Progesterone Production by dispersed luteal cells. 81 45

Renin gene expression in the mouse kidney and submandibular gland (SMG) are differentially regulated by cAMP. In this study, we examined the potential molecular mechanism responsible for this tissue-specific regulation. 32P end-labeled synthetic oligonucleotide containing mouse renin cAMP-responsive element (CRE) was incubated with kidney nuclear extracts from either control or cAMP-treated mice and analyzed by gel mobility shift assay. Our results demonstrated that cAMP induced a nuclear protein which complexed with the CRE oligonucleotide in a specific manner. This nuclear protein-DNA binding was competed effectively by the oligonucleotide containing human chorionic gonadotropin alpha-subunit CRE but not by the mouse renin DNA fragment from which the CRE was deleted by site-directed mutagenesis. In contrast, no DNA-protein complex formation could be detected when this [32P]CRE oligonucleotide was incubated with the SMG nuclear extract from control or cAMP-treated mice. However, CRE-binding protein complex formation was demonstrated in the SMG nuclear extract when the incubation was performed in the presence of 0.8% sodium deoxycholate and 1.2% Nonidet P-40, detergents that dissociate protein-protein complexes. Furthermore, in the absence of deoxycholate, we observed that SMG nuclear extract attenuated the binding of the kidney CRE-binding protein to mouse renin CRE in a dose-dependent manner and this inhibitory effect of SMG nuclear extract disappeared in the presence of sodium deoxycholate. This inhibitory nuclear protein in SMG is specific for CRE-binding protein since it does not affect nuclear protein binding to synthetic DNA oligonucleotides of human collagenase AP-1 and human metallothionein AP-2. Our data further suggest that inhibitory nuclear protein is present in lower quantities in other extrarenal tissues, i.e. testes, liver, brain, heart, but is not detectable in the kidney. Taken together, these results suggest that the SMG and certain extrarenal tissues contain nuclear trans-acting factor(s) that interact with CRE-binding protein, thereby interfering with its binding to mouse renin CRE. The presence of this inhibitory protein in the mouse SMG nucleus may contribute to the tissue-specific regulation of the renin gene expression by cAMP.
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PMID:Molecular mechanism of tissue-specific regulation of mouse renin gene expression by cAMP. Identification of an inhibitory protein that binds nuclear transcriptional factor. 165 39

Oestrous rats and golden hamsters were anesthetized with pentobarbital, one of the femoral arteries and veins and one of the ovarian veins were cannulated. Blood fractions were collected from the ovary. After the first two fractions synthetic adrenocorticotropic hormone (ACTH) or human chorionic gonadotropin (hCG) was injected i.v. Blood pressures and ovarian blood flow were continuously recorded. Progesterone (P) and oestradiol-17 beta (E2) were determined from the ovarian venous blood by radioimmunoassay (RIA). ACTH induced a temporary elevation in the ovarian blood flow, P and E2 secretion both in rats and hamsters. In rats and hamsters hCG induced a continuous elevation in P secretion but the ovarian blood flow and E2 secretion remained unchanged. Luteal cells from pseudopregnant rats or oestrous hamsters were dispersed with collagenase and incubated with ACTH or hCG. A sample of the cells was preincubated with polymixin-B, indomethacin or ibuprofen. P and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) contents of the medium and cyclic 3,5 adenosine monophosphate (cAMP) content of the cells were determined by RIA. ACTH stimulated the release of 6-keto-PGF1 alpha and the secretion of P from the luteal cells of both species, which was inhibited by indomethacin or ibuprofen, but ACTH did not alter the cAMP content of luteal cells. The polymixin-B prevented ACTH to stimulate P secretion, but it did not elevate the 6-keto-PGF1 alpha release, while the cAMP content of the cells remained unchanged. It is supposed that the polyphosphoinositol-Ca(2+)-protein kinase-C second messenger system is involved in the ACTH induced stimulation of P secretion.
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PMID:Action of ACTH in the luteal ovary. 166 58

This study was designed to determine the effects of 17 beta-estradiol (E2) on Leydig cell development in the rat. Mature (60 to 65 days old) male rats received a single intraperitoneal injection of ethane dimethylsulfonate (EDS, 100 mg/kg body weight); untreated rats served as controls. In one series of experiments, groups of EDS-treated rats also received daily injections of either E2 (25 micrograms/100 g body weight), human chorionic gonadotropin (hCG, 20 IU/day), a combination of the two, or vehicle only (EDS controls). Animals were killed on days 2, 4, 10, 16, 24, 30, and 36 after EDS treatment. In another series of experiments, groups of EDS-treated rats received daily injections of hCG and E2 during days 0 through 5, 5 through 30, or 16 through 30 after EDS treatment, and were killed on day 30. In both series of experiments, the steroidogenic capacity and hCG binding capacity of the Leydig cells were examined in short-term in vitro incubations using collagenase-dispersed interstitial cells. Testes were also prepared and examined histologically by light and electron microscopy. E2 treatment of animals during the initial 5 days after EDS administration had no effect on the regeneration of interstitial cells and Leydig cells. Treatment with E2 during days 5 to 30 post-EDS blocked the regeneration of Leydig cells and thereby significantly reduced the increase in interstitial cell numbers. Finally, when E2 treatment was delayed until 16 days post-EDS, there was no significant reduction in the regeneration of interstitial or Leydig cells. These data suggest that an important developmental process that is necessary for Leydig cell regeneration occurs between days 5 and 16 post-EDS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:17 beta-estradiol inhibition of Leydig cell regeneration in the ethane dimethylsulfonate-treated mature rat. 166 73

Gene regulation by steroid hormones is accomplished by a variety of different mechanisms leading to induction or repression of particular genes. These mechanisms are all mediated by a single class of intracellular hormone receptors, which in the unliganded state are maintained in an inactive form by association with other cellular proteins, including hsp90. Induction of the mouse mammary tumor virus (MMTV) requires binding of the hormone receptor to a hormone-responsive element (HRE) that is precisely organized in a phased nucleosome. After receptor binding, changes in chromatin structure are detected that correlate with binding of transcription factors, including nuclear factor I, to the MMTV promoter. However, although nuclear factor I acts as a basal transcription factor on the MMTV promoter it does not cooperate with the hormone receptors in terms of binding to free DNA, and mutation of the nuclear factor I binding site does not eliminate hormonal stimulation. This residual induction is mediated by octamer motifs upstream of the TATA box that bind the ubiquitous transcription factor OTF-1. Mutation of these octamer motifs does not influence basal transcription in vitro, but completely abolishes the stimulatory effect of progesterone receptor. Glucocorticoids also inhibit expression of many genes. The effect on the gene for the alpha-subunit of chorionic gonadotropin is due to DNA binding competition between the receptor and the protein mediating cAMP induction, whereas repression of the collagenase gene involves an interaction of the receptor with components of the AP1 complex, Jun and Fos.
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PMID:Transcriptional control by nuclear receptors. 201 57

Plasmids that encode a bioactive amino-terminal fragment of the heat-stable inhibitor of the cAMP-dependent protein kinase, PKI(1-31), were employed to characterize the role of this protein kinase in the control of transcriptional activity mediated by three DNA regulatory elements in the JEG-3 human placental cell line. The 5'-flanking sequence of the human collagenase gene contains the heptameric sequence, 5'-TGAGTCA-3', previously identified as a "phorbol ester" response element. Reporter genes containing either the intact 1.2-kilobase 5'-flanking sequence from the human collagenase gene or just the 7-base pair (bp) response element, when coupled to an enhancerless promoter, each exhibit both cAMP and phorbol ester-stimulated expression in JEG-3 cells. Cotransfection of either construct with plasmids encoding PKI(1-31) inhibits cAMP-stimulated but not basal- or phorbol ester-stimulated expression. Pretreatment of cells with phorbol ester for 1 or 2 days abrogates completely the response to rechallenge with phorbol ester but does not alter the basal expression of either construct; cAMP-stimulated expression, while modestly inhibited, remains vigorous. The 5'-flanking sequence of the human chorionic gonadotropin-alpha subunit (HCG alpha) gene has two copies of the sequence, 5'-TGACGTCA-3', contained in directly adjacent identical 18-bp segments, previously identified as a cAMP-response element. Reporter genes containing either the intact 1.5 kilobase of 5'-flanking sequence from the HCG alpha gene, or just the 36-bp tandem repeat cAMP response element, when coupled to an enhancerless promoter, both exhibit a vigorous cAMP stimulation of expression but no response to phorbol ester in JEG-3 cells. Cotransfection with plasmids encoding PKI(1-31) inhibits both basal and cAMP-stimulated expression in a parallel fashion. The 5'-flanking sequence of the human enkephalin gene mediates cAMP-stimulated expression of reporter genes in both JEG-3 and CV-1 cells. Plasmids encoding PKI(1-31) inhibit the expression that is stimulated by the addition of cAMP analogs in both cell lines; basal expression, however, is inhibited by PKI(1-31) only in the JEG-3 cell line and not in the CV-1 cells. These observations indicate that, in JEG-3 cells, PKI(1-31) is a specific inhibitor of kinase A-mediated gene transcription, but it does not modify kinase C-directed transcription.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Plasmids encoding PKI(1-31), a specific inhibitor of cAMP-stimulated gene expression, inhibit the basal transcriptional activity of some but not all cAMP-regulated DNA response elements in JEG-3 cells. 247 35

To assess the role of inhibitors of proteolytic enzymes, such as plasminogen activator (PA) and collagenase in the ovulatory process, inhibitor activity and mRNA levels were examined in periovulatory rat and human ovaries. In the rat, immature animals received 20 IU of pregnant mare serum gonadotropin (PMSG) followed 52 h later by 10 IU of hCG. Ovaries were removed at intervals from 0 to 20 h after human chorionic gonadotropin (hCG) administration. Inhibitor activity for metalloproteinases, such as collagenase, increased from 60.5 +/- 4.1 inhibitor units/ovary at 0 h (i.e., time of hCG treatment) to a maximum of 218.2 +/- 11.4 units/ovary at 8 h after hCG before decreasing at 12 h (time of ovulation) and 20 h (122.2 +/- 7.9 and 71.6 +/- 8.1 units/ovary, respectively). Human follicular fluid and granulosa cells were obtained from preovulatory follicles of patients in our in vitro fertilization program. Metalloproteinase inhibitor activity was evaluated in follicular fluid as well as the levels of PA and PA inhibitor (PAI) mRNA by Northern analysis. Increasing metalloproteinase inhibitor activity was positively correlated with follicular levels of estradiol (p less than 0.001) and progesterone (p less than 0.02, N = 26). Chromatographic separation of follicular fluid resulted in two peaks of metalloproteinase inhibitor activity. The large molecular weight (MW) inhibitor had an approximate size of 700 kilodaltons (kDa) and may represent alpha 2-macroglobulin, a serum-derived inhibitor. The small MW inhibitor shared many of the characteristics of tissue-derived inhibitors of metalloproteinases. Partial purification of the small MW inhibitor by Concanavalin A-Sepharose and Heparin-Sepharose chromatography demonstrated the inhibitor to be a glycoprotein with an approximate MW = 28-29 K. Northern analysis of human granulosa cell total RNA from preovulatory follicles showed little or no detectable tissue-type PA or urokinase-type PA mRNA. In contrast, two species of PA inhibitor type-1 mRNA were detected in relative abundance. The present findings demonstrate the presence of proteolytic inhibitors in periovulatory ovaries of the rat and human. These ovarian inhibitors may play a role in regulating connective tissue remodeling during follicular rupture.
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PMID:The role of ovarian proteases and their inhibitors in ovulation. 255 99


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