Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.25.1 (deoxyribonuclease)
 1,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently purified a novel pituitary polypeptide, designated 7B2. Subsequently, we developed a sensitive and specific radioimmunoassay (RIA) for this novel polypeptide. Our aim in the present study was to investigate the release of 7B2 from rat pituitary induced by various hypothalamic factors [luteinizing hormone-releasing factor (LH-RH), corticotropin-releasing factor (CRF), and growth hormone-releasing factor (GRF)]. The anterior pituitaries were removed from rats and immediately dispersed enzymatically (a mixture of collagenase/dispase/deoxyribonuclease/chicken serum) and plated on collagen-coated multiwell plates in culture medium containing 10% fetal bovine serum. After 2 days of attachment period, the medium was replaced with fresh medium every 24 h. The primary cell culture was incubated with various concentrations of LH-RH, CRF or GRF. Subsequently, the concentrations of IR-7B2, IR-LH, IR-FSH, and IR-ACTH released into the medium were quantified by specific RIA. LH-RH, at a concentration as low as 7.5 ng/ml (6 X 10(9) M: dose range 7.5-60 ng/ml) stimulated the release of IR-7B2, IR-LH, and IR-FSH, by 2- to 3-fold, 17- to 18-fold, and 3-fold, respectively, over basal levels. No significant increase of IR-7B2 was observed when stimulated by CRF or GRF at doses as high as 100 ng/ml. In addition, K+ (50 mM) stimulated the release of all the peptides measured. In conclusion, our studies suggest that the novel peptide 7B2 is under LH-RH control and indirectly confirm the immunohistochemical results of its cellular co-localization in FSH and LH cells.
 ...
PMID:Specific release of a novel pituitary polypeptide, 7B2, from rat anterior pituitary cells in vitro by luteinizing hormone-releasing hormone. 310 Sep 76

Activin has been previously demonstrated to directly stimulate the synthesis of GnRH receptors and to increase FSH secretion in non-human pituitary cell cultures (PCC). Several results in Macaque monkeys failed to support an unequivocal role for Inhibin in FSH suppression. Whereas the bioactivity of Inhibin and Activin has been demonstrated in rat PCC, no data exist on human pituitary response to these peptides. We studied, therefore, the secretion of FSH and LH by dispersed human fetal PCC from > 140 midtrimester abortions in response to recombinant human (rh-) Activin-A, Inhibin, and other secretagogues. After mechanical and enzymatic dispersion, using collagenase and deoxyribonuclease, the human fetal pituitary cells were cullured on extracellular matrix (ECM) like material coaled 24 well plate (Primaria, Falcon) in fetal calf serum-containing medium. After 3 days incubation in serum-containing medium, the PCC were washed and preincubated for 90 mins in serum-free medium and incubated with rh-ActivinA, Inhibin, TGF-p, Follistatin, sex steroids, and GnRH in quadruplicate wells. The EC50 of rh-Activin-A for FSH secretion was ~ 10 ng/mL. rh- Activin-A was a more potent secretagogue for FSH secretion than GnRH. On the contrary, GnRH (20 ng/mL) was more potent than rh-Activin A for LH secretion. Nevertheless, a significant increase in LH secretion into the medium was brought about by rh-Activin-A. Inhibin decreased FSH secretion but LH response to Inhibin was inconsistent. GnRH opposed the inhibitory effect of Inhibin on both gonadotropins. In dynamic, short term, repetitive exposure of fetal pituitary fragments to rh-Activin-A (superfusionl we could not receive -a similar increase in LH & FSH as in static incubations, as opposed to a short GnRH exposure. Melatonin did not inhibit LH secretion in human PCC as opposed to rodents. In addition to their endocrine, paracrine, and sutocrine effects and to their role as possible markers, the TGF-b superfamily members may atiect embryogenesis and possibly immunomodulation of the fetus. In contrast to others, who could detect Inhibin-B only in male but not in female fetuses sera, we have measured Inhibin-B in both male and female midtrimester fetal sera, challenging the previous assumption that the fetal origin is only Sertoli cells. Human fetal PCC express the previously reported physiologic responses to Activin and Inhibin generated in non-human experiments on gonadotropin secretion in-vitro, and may serve as a physiologic model for studying human gonadotrope responses to the TGF-b family of peptides. Our preliminary data may provide the first unequivocal evidence for the validity of the Activin/Inhibin hypothesis in human.
 ...
PMID:Response of human fetal pituitary cells to activin, inhibin, hypophysiotropic and neuroregulatory factors in vitro. 1175 7

The number of female germ cells in pig fetuses decreases by 70% between day 50 after mating and day 300 after birth. Approximately 55% of antral follicles undergo degeneration (atresia) except during the 3 days before oestrus, when only 15% of the follicles survive to ovulate. Apoptosis, a form of programmed cell death, is recognized as the mechanism of germ cell death and follicle atresia at all stages of folliculogenesis. The internucleosomal cleavage of genomic DNA caused by caspase-induced deoxyribonuclease activity was measured in pig granulosa cells by DNA fluorescence flow cytometry, densitometry of fluorescently labelled internucleosomal DNA fragments and immunohistochemical analysis of the 3' end labelling of deoxyribonuclease-nicked DNA on frozen tissue sections. Follicular atresia during the 3 days before oestrus is associated with a 60-70% decrease in the secretion of FSH. In granulosa cells, apoptosis is associated with decreased cell proliferation and reduced production of oestradiol and inhibin. In cultured pig granulosa cells, FSH and IGF-I are anti-apoptotic and a caspase inhibitor blocked apoptosis, thereby providing evidence of caspase activity. Oocytes in most follicles have resumed meiotic maturation; therefore, one role for apoptosis and follicle atresia may be to act as a barrier to ovulation of oocytes that have not remained in meiotic arrest.
 ...
PMID:Apoptosis during folliculogenesis in pigs. 1198 Jan 88

Cyclin D2 (Ccnd2) is an essential gene for folliculogenesis, as null mutation in mice impairs granulosa cell proliferation in response to FSH. Ccnd2 mRNA is induced during the estrus cycle by FSH and is rapidly inhibited by LH. Yet, the responsive elements and transcription factors accounting for the gene expression of cyclin D2 in the ovary have not been fully characterized. Using primary cultures of rat granulosa cells and immortalized mouse granulosa cells, we demonstrate a mechanism for the regulation of cyclin D2 at the level of transcription via a PKA-dependent signaling mechanism. The promoter activity of cyclin D2 was shown to be induced by FSH and the catalytic alpha subunit of PKA (PRKACA), and this activity was repressible by inducible cAMP early repressor (ICER), a cAMP response element (CRE) modulator isoform. In silico analysis of the mouse, rat, and human cyclin D2 promoters identified two CRE-binding protein sites, a conserved proximal element and a less conserved distal element relative to the translation start site. The mutation on the proximal element drastically decreases the effects of PRKACA and ICER on the promoter activity, whereas the mutation on the distal element did not contribute to the decrease in the promoter activity. Electrophoretic mobility shift assays and deoxyribonuclease footprint analysis confirmed ICER binding to the proximal element, and chromatin immunoprecipitation analysis demonstrated the occurrence of this binding in vivo. These results showed a CRE within the upstream region of Ccnd2 that is (at least partly) implicated in the stimulation and repression of cyclin D2 transcription. Finally, our data suggest that ICER involvement in the regulation of granulosa cell proliferation as overexpression of ICER results in the inhibition of PRKACA-induced DNA synthesis.
 ...
PMID:Transcriptional regulation of cyclin D2 by the PKA pathway and inducible cAMP early repressor in granulosa cells. 1662 3