Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bisphenol-A (BPA) is used to produce polymers for production of polycarbonate and epoxy resins that are used in food containers and dental appliances. BPA binds to estrogen receptors and induces estrogenic activity in a number of biological systems. We recently reported that although Fisher 344 (F344) and Sprague-Dawley (S-D) rat strains exhibit different sensitivities to BPA at the level of vaginal epithelial cell proliferation, there was no difference in immediate early proto-oncogene expression between the two animal strains. In the present study we investigated the effects of BPA on expression of another estrogen-target gene, vascular endothelial growth factor (VEGF), in the uterus, vagina, and pituitary of F344 and S-D rats. Adult rats were ovariectomized and treated with BPA by intraperitoneal injection at concentrations of 0.02 to 150 mg/kg body wt. Expression of VEGF was monitored by RNase protection assay at 2 hr after treatment. There was a significant effect of dose of BPA on the type of VEGF isoform expressed in the uterus, vagina, and pituitary. BPA induced greater (P < 0.01) levels of VEGF164 and VEGF120+188 than VEGF110 levels. The lowest BPA dose that had a significant (P< 0.05) effect on VEGF expression compared with vehicle treatment was 37.5 mg/kg body wt.; dose-response curves did not differ between strains. This is the first report that the primary response of the uterus, vagina, and pituitary to BPA includes rapid induction of VEGF expression. Due to the capacity of VEGF to engage pleiotropic signaling pathways in other cellular systems, we suggest that modulation of VEFG may play a role in establishing the response of estrogen-target organs to estrogenic xenobiotics.
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PMID:Effects of the xenoestrogen bisphenol A on expression of vascular endothelial growth factor (VEGF) in the rat. 1139 78

The skin, the largest organ in the human body, is composed of a series of androgen-sensitive components that all express the steroidogenic enzymes required to transform dehydroepiandrosterone (DHEA) into dihydrotestosterone (DHT). In fact, in post-menopausal women, all sex steroids made in the skin are from adrenal steroid precursors, especially DHEA. Secretion of this precursor steroid by the adrenals decreases progressively from the age of 30 years to less than 50% of its maximal value at the age of 60 years. DHEA applied topically or by the oral route stimulates sebaceous gland activity, the changes observed being completely blocked in the rat by a pure antiandrogen while a pure antiestrogen has no significant effect, thus indicating a predominant or almost exclusive androgenic effect. In human skin, the enzyme that transforms DHEA into androstenedione is type 1 3beta-hydroxysteroid dehydrogenase (type 1 3beta-HSD) as revealed by RNase protection and immunocytochemistry. The conversion of androstenedione into testosterone is then catalyzed in the human skin by type 5 17beta-HSD. All the epidermal cells and cells of the sebaceous glands are labelled by type 5 17beta-HSD. This enzyme is also present at a high level in the hair follicles. Type 1 is the 5alpha-reductase isoform responsible in human skin for the conversion of testosterone into DHT. In the vagina, on the other hand, DHEA exerts mainly an estrogenic effect, this effect having been demonstrated in the rat as well as in post-menopausal women. On the other hand, in experimental animals as well as in post-menopausal women, DHEA, at physiological doses, does not affect the endometrial epithelium, thus indicating the absence of DHEA-converting enzymes in this tissue, and avoiding the need for progestins when DHEA is used as hormone replacement therapy.
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PMID:Intracrinology and the skin. 1159 10

Sperm adhesion molecule 1 (Spam1) is a widely conserved sperm surface protein with multiple roles in mammalian fertilization. Although the gene for this protein has been thought to be testis specific based on Northern blot analysis, there is evidence for nontesticular expression when transcripts are analyzed by more sensitive techniques. In the present investigation, results of a reverse transcription polymerase chain reaction assay, an RNase-protection assay (RPA), and an in situ transcript hybridization assay revealed that the murine Spam1 gene is transcribed in the female genital tract. RPA revealed that Spam1 transcripts are synthesized in a region-dependent manner, with the oviduct having lower transcript levels than the uterus and vagina. The transcripts levels were 3- to 10-fold lower in the female genital tract than in the testis. In situ transcript hybridization assay revealed RNA in the luminal epithelium in all three regions of the genital tract and in the uterine myometrium and the oviductal mesothelium. Western blot analysis and immunohistochemistry demonstrated that the protein concentration is 1.5- to 3-fold lower in female tissues than in sperm, and localization is similar to that of the transcripts. The protein has hyaluronidase activity at neutral pH, which is unique for sperm hyaluronidase, but not at acidic pH. In the uterus, Spam1 expression fluctuated during the estrous cycle. Its localization suggests that in addition to functioning as a secretory protein, it may be involved in hyaluronic acid metabolism or turnover in the female genital tract. Our results provide further evidence that Spam1 is a multifunctional protein and that it is less restricted in its expression than previously reported.
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PMID:Mouse Spam1 (PH-20) is a multifunctional protein: evidence for its expression in the female reproductive tract. 1267 66

This study aimed to determine the effect of bull seminal plasma (SP) and sperm on endometrial function. Bovine endometrial explants were incubated with: ejaculated sperm with or without SP, epididymal sperm, or SP alone. Neither ejaculated nor epididymal sperm induced differential expression of IL1A, IL1B, IL6, IL8, PTGES2, TNFA, and LIF. Interestingly, SP had a detrimental effect on endometrial RNA integrity. Addition of an RNase inactivation reagent to SP blocked this effect, evidencing a role for a SP-RNase. Because bulls deposit the ejaculate in the vagina, we hypothesized that the bovine endometrium is more sensitive to SP-RNase than vaginal and cervical tissues (which come into contact with SP during mating), or to endometrium from intrauterine ejaculators (such as the horse). In addition, due to differences in SP-RNase abundance depending on SP collection method (i.e., with an artificial vagina, AV, or by electroejaculation, EE), this effect was also tested. Bull SP, collected by AV, degrades RNA of mare endometrium, and bovine vagina, cervix and endometrium. However, stallion SP or bull SP collected by EE did not elicit this effect. Thus, results do not support a role for SP in modulating endometrial function to establish pregnancy in cattle.
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PMID:Species-specific and collection method-dependent differences in endometrial susceptibility to seminal plasma-induced RNA degradation. 3163 62

Gynecologic sarcomas are uncommon neoplasms, the majority occurring in the uterus. Due to the diverse nature of these, the description of "new" morphological types and the rarity of some of them, pathological diagnosis and treatment is often challenging. Finding genetic alterations specific to, and frequently occurring, in a certain type can aid in the diagnosis. DICER1 is a highly conserved ribonuclease crucial in the biogenesis of microRNAs and mutations in DICER1 (either somatic or germline) have been detected in a wide range of sarcomas including genitourinary embryonal rhabdomyosarcomas (ERMS) and adenosarcomas. Importantly, DICER1-associated sarcomas share morphological features irrespective of the site of origin such that the pathologist can strongly suspect a DICER1 association. A review of the literature shows that almost all gynecologic ERMS reported (outside of the vagina) harbor DICER1 alterations, while approximately 20% of adenosarcomas also do so. These two tumor types exhibit significant morphological overlap and DICER1 tumor testing may be helpful in distinguishing between them, because a negative result makes ERMS unlikely. Given that germline pathogenic DICER1 variants are frequent in uterine (corpus and cervix) ERMS and pathogenic germline variants in this gene cause a hereditary cancer predisposition syndrome (DICER1 syndrome), patients diagnosed with these neoplasms should be referred to medical genetic services. Cooperation between pathologists and geneticists is crucial and will help in improving the diagnosis and management of these uncommon sarcomas.
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PMID:DICER1-associated embryonal rhabdomyosarcoma and adenosarcoma of the gynecologic tract: Pathology, molecular genetics, and indications for molecular testing. 3313 84