Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a longitudinal study of 82 children we found a gradual rise in median plasma concentrations of 11 beta-hydroxyandrostenedione (11 beta-OH-A4) from 2.5 to 6.4 nmol/l during childhood which was similar in both sexes. This could reflect changes in adrenal function during the adrenarche and sexual maturation. Plasma concentrations of 11 beta-OH-A4 in adults follow the patterns of cortisol secretion. In patients with diseases of the adrenal cortex, the plasma concentrations of 11 beta-OH-A4 were consistent with the pathology of each condition. In women with polycystic ovaries (PCO) undergoing gonadotrophic stimulation for in vitro fertilization and embryo transfer, 11 beta-OH-A4 (median = 3.8 nmol/l), testosterone and androstenedione, were raised when compared to women with normal ovaries (11 beta-OH-A4 median = 2.6 nmol/l). Follicular fluid has concentrations of 11 beta-OH-A4 six to twelve times greater than plasma levels and in women with PCO, 11 beta-OH-A4 concentrations were lower than in women with normal ovaries, which is consistent with an inhibition of ovarian 11 beta-hydroxylase. Granulosa cells in vitro demonstrated the production of 11 beta-OH-A4 by side chain cleavage of cortisol. These data support an adrenal source for 11 beta-OH-A4 but the raised plasma concentrations in women with polycystic ovary syndrome (PCOS) may reflect the excess androgen output from the ovary. 11 beta-OH-A4 may therefore be an additional marker for ovarian dysfunction.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Studies to confirm the source of 11 beta-hydroxyandrostenedione. 153 6

The mechanism of the ovarian dysfunction in polycystic ovary syndrome, the most common cause of anovulatory infertility, remains obscure. Clinical data suggest that follicle stimulating hormone (FSH) action may be inhibited at the ovarian level by paracrine factors derived, presumably, from interstitial cells. The greater responsiveness to FSH of granulosa cells isolated from polycystic ovaries (PCO) compared with that seen in cells derived from normal ovaries, provides some support for this hypothesis and we present data which suggests that epidermal growth factor, or more likely transforming growth factor alpha, could be a candidate for this inhibitor. It should be emphasized, however, that the cardinal biochemical feature of the PCO is hypersecretion of androgens by interstitial cells. Stromal tissue from the PCO will secrete significant quantities of androstenedione in response to LH, whereas there is a negligible response in stroma from normal ovaries. It remains to be determined whether androgens have a direct inhibitory effect on FSH-induced oestradiol production in the human follicle, or whether they might exert an indirect effect by activating inhibitory polypeptide growth factors.
J Steroid Biochem Mol Biol 1991
PMID:Polycystic ovary syndrome: interaction of follicle stimulating hormone and polypeptide growth factors in oestradiol production by human granulosa cells. 195 41

The present study was conducted to examine the expression of tumor necrosis factor-alpha (TNF-alpha) and its receptors (types I and II, designated TNFR-I and TNFR-II, respectively) in human oocytes and cumulus cells at the mRNA and protein levels. mRNA expression was investigated using a reverse transcriptase-polymerase chain reaction (PCR)/Southern hybridization procedure. DNA-free RNA was isolated from the oocytes/cumulus cells, reverse-transcribed, and PCR-amplified using specific oligonucleotide primers based upon genomic/cDNA sequences. The expected bands of 303 bp and 513 bp were observed in oocytes and cumulus cells using primers based on genomic/cDNA sequences of TNF-alpha and TNFR-II, respectively, that hybridized with specific cDNA probes in Southern blot hybridization procedure. The expected band of 368 bp was not observed in oocytes and cumulus cells using primers based on the TNFR-I cDNA sequence. Similar results were observed for expression at the protein level, as seen by the immunoreactivity of the specific antibodies with the paraformaldehyde-fixed oocytes and cumulus cells in the indirect immunofluorescence technique (IFT). These results indicate that human oocytes and cumulus cells express TNF-alpha and its receptor type II (TNFR-II), and not type I (TNFR-I), both at the mRNA and protein levels. These findings provide further evidence and substantiate the proposed physiologic role of TNF-alpha in ovarian function, and may lead to clinical applications in in vitro fertilization programs and in diagnosis and treatment of infertility in women, especially in cases attributed to ovarian dysfunction.
Mol Reprod Dev 1997 Jun
PMID:Expression of tumor necrosis factor-alpha and its receptors type I and type II in human oocytes. 913 12

The concept of a safe, immunocontraceptive vaccine using the zona pellucida glycoprotein 3 (ZP3) as an immunogen has been marred by the appearance of ovarian dysfunction in several species. However, careful selection of epitopes on mouse ZP3 have demonstrated that it is possible to segregate contraceptive bone marrow-derived (B)-cell epitopes from the cytotoxic thymus-derived (T)-cell epitopes thought to be responsible for inducing ovarian disease. B-cell epitopes on marmoset ZP3 (mstZP3) were identified by epitope mapping studies. Using a panel of polyclonal antibodies against recombinant mstZP3, an immunodominant epitope mstZP3(301-320) was identified. A chimeric peptide was co-linearly synthesized incorporating this sequence with a promiscuous tetanus toxoid T-helper cell epitope. Using the common marmoset (Callithrix jacchus) as an animal model, we have compared the consequences of active immunization with homologous recombinant mstZP3 and mstZP3(301-320) chimeric peptide vaccine. Long-term infertility was achieved using mstZP3 but at the expense of ovarian function. In contrast, no disruption to ovarian function was observed following mstZP3(301-320) immunization. Antibodies to this peptide immunolocalized to the zona pellucida of both marmoset and human ovarian sections and inhibited human sperm-zona binding by approximately 60% in vitro. However, in-vivo studies indicated that targeting a single ZP3 epitope was insufficient to reliably and consistently achieve a contraceptive effect.
Mol Hum Reprod 1999 Apr
PMID:Design and evaluation of a ZP3 peptide vaccine in a homologous primate model. 1032 6

Female rats at weaning (30 days age) were maintained on vitamin E-deficient diet for 70 days. The vitamin E-deficient and control animals were sacrificed on 100 days of age. To study recovery a group of animals were supplemented with normal diet for last 25 days after initial 45 days of deficient diet or vice versa. The most striking data found were (i) significant drop in uterine weight in deficient group (ii) significant decrease in estrogen, LH and estrogen-induced uterine enzymes alkaline phosphatase and peroxidase and (iii) ovarian dysfunction as noted by degenerating graffian follicles. The significance of these findings is discussed in this report.
Mol Cell Biochem 1999 Aug
PMID:Vitamin E-deficiency induced changes in ovary and uterus. 1049 90

To minimize ovarian dysfunction subsequent to immunization with zona pellucida (ZP) glycoproteins, synthetic peptides encompassing the antigenic B cell epitopes as immunogens have been proposed. In this study, attempts have been made to clone and express a recombinant chimeric protein encompassing the epitopes corresponding to bonnet monkey (Macaca radiata) ZP glycoprotein-1 (bmZP1, amino acid residues 132-147), ZP glycoprotein-2 (bmZP2, amino acid residues 86-113), and ZP glycoprotein-3 (bmZP3, amino acid residues 324-347). The above chimeric recombinant protein (r-bmZP123) was expressed as a polyhistidine fusion protein in Escherichia coli. Immunoblot with murine monoclonal antibody, MA-813, generated against recombinant bmZP1 revealed a major band of approximately 10 kDa. The r-bmZP123 was purified on nickel-nitrilotriacetic acid resin under denaturing conditions. The female rabbits immunized with purified r-bmZP123 conjugated to diphtheria toxoid (DT) generated antibodies that reacted with r-bmZP123 and DT in an ELISA. In addition, the immune sera also reacted with E. coli expressed recombinant bmZP1, bmZP2, and bmZP3. In an indirect immunofluorescence assay, the antibodies against r-bmZP123 recognized native ZP of bonnet monkey as well as human. The immune sera also inhibited, in vitro, the binding of human spermatozoa to the human zona in the hemizona assay (HZA). These studies, for the first time, demonstrate the feasibility of assembling multiple epitopes of different ZP glycoproteins as a recombinant protein that elicit antibodies which are reactive with native zona and also inhibit, in vitro, human sperm-oocyte binding.
Mol Reprod Dev 2003 Jul
PMID:Efficacy of antibodies against Escherichia coli expressed chimeric recombinant protein encompassing multiple epitopes of zona pellucida glycoproteins to inhibit in vitro human sperm-egg binding. 1278 53

In the present study, the porcine zona pellucida (ZP)-3alpha eukaryotic expression vector pVAX1-pZP3alpha was constructed by genetic recombinant technology, then the recombinant plasmid was encapsulated in nanoparticles with chitosan, and the imaging of chitosan/pVAX1-pZP3alpha nanoparticles by Atomic Force Microscope (AFM) was processed. Feeding mouse with those microencapsulation by gastric larvae, and after 5 days, detecting its expression in mouse intestine by RT-PCR and indirect immunofluorescence (IIF). Results show that the porcine ZP-3alpha eukaryotic expression vector pVAX1-pZP3alpha had been constructed correctly, and the chitosan-DNA expressing ZP microencapsulation was prepared successfully. After 5 days of feeding mouse, the transcription and expression of those DNA vaccines were found in mouse alvine chorion. The preparation of chitosan/pVAX1-pZP3alpha plasmid DNA nanoparticles and its expression in mice will help to investigate the feasibility of ZP DNA vaccine to induce oviduct local mucosal immunity against ZP to block the fertilization without causing ovarian dysfunction, which will provide new ideas and ways for research and exploiting more effective, more convenient oral contraceptive vaccines.
Mol Reprod Dev 2004 Jun
PMID:Preparation of chitosan-plasmid DNA nanoparticles encoding zona pellucida glycoprotein-3alpha and its expression in mouse. 1509 39

Polycystic ovary syndrome (PCOS) represents the most common cause of anovulatory infertility and affects 5-10% of women of reproductive age. The etiology of PCOS is still unknown. The current study is the first to describe consistent differences in gene expression profiles in human ovaries comparing PCOS patients vs. healthy normoovulatory individuals. The microarray analysis of PCOS vs. normal ovaries identifies dysregulated expression of genes encoding components of several biological pathways or systems such as Wnt signaling, extracellular matrix components, and immunological factors. Resulting data may provide novel clues for ovarian dysfunction in PCOS. Intriguingly, the gene expression profiles of ovaries from (long-term) androgen-treated female-to-male transsexuals (TSX) show considerable overlap with PCOS. This observation provides supportive evidence that androgens play a key role in the pathogenesis of PCOS. Presented data may contribute to a better understanding of dysregulated pathways in PCOS, which might ultimately reveal novel leads for therapeutic intervention.
Mol Endocrinol 2004 Dec
PMID:Abnormal gene expression profiles in human ovaries from polycystic ovary syndrome patients. 1530 91

Inhibin B is predominantly produced by early healthy antral follicles during the luteo-follicular transition of the menstrual cycle. High inhibin B concentrations during the early follicular phase are responsible for the decline in FSH serum levels closing the FSH window and assuring single dominant follicle selection in the human. Early follicular phase inhibin B levels decrease over time, reflecting the recruitment of a diminished cohort of follicles with ovarian ageing. Hence, inhibin B is a predictor of poor response in IVF. In patients with PCOS inhibin B levels (potentially representing the number of healthy, early antral follicles) may be associated with the severity of ovarian dysfunction and consequently may predict ovulation induction outcome. However, inhibin B levels are normal in most PCOS patients suggesting a normal number of healthy follicles despite an increase in overall follicle number. Recent findings indicate that initial inhibin B concentrations can not predict the outcome of ovulation induction by either clomiphene citrate or FSH. Finally, inhibin B levels decrease over time in PCOS.
Mol Cell Endocrinol 2004 Oct 15
PMID:Inhibins and adult ovarian function. 1545 66

Immunocontraception achieved by immunization with zona pellucida (ZP) glycoproteins is invariably associated with ovarian dysfunction. Use of ZP glycoprotein-based synthetic peptides as immunogens has been proposed to overcome adverse side effects on ovaries. In the present study, a chimeric peptide encompassing the epitopes of bonnet monkey (Macaca radiata) ZP glycoprotein-1 (bmZP1; amino acid residues 251-273) and ZP glycoprotein-3 (bmZP3; amino acid residues 324-347), separated by a tri-glycine spacer, was synthesized and conjugated to diphtheria toxoid (DT). Immunization of female BALB/cJ mice and bonnet monkeys with the chimeric peptide led to generation of antibodies that reacted with the chimeric peptide, individual bmZP1 & bmZP3 peptides, and also recombinant bmZP1 and bmZP3 proteins expressed by E. coli in an ELISA. Indirect immunofluorescence studies revealed that the immune serum also recognized human as well as bonnet monkey ZP. A significant inhibition of human sperm binding to ZP was observed with antibodies generated against the chimeric peptide in mice (P = 0.0001) as well as monkeys (P = 0.0002) in a hemizona assay (HZA). The inhibition efficacy was significantly higher than that observed by using antibodies against the individual bmZP1 and bmZP3 peptides. Interestingly, no ovarian pathology was observed in female bonnet monkeys immunized with the chimeric peptide. These studies have demonstrated that the chimeric peptide encompassing peptides of multiple ZP glycoproteins may be a promising candidate antigen for designing immunocontraceptive vaccines.
Mol Reprod Dev 2005 Mar
PMID:Efficacy of antibodies against a chimeric synthetic peptide encompassing epitopes of bonnet monkey (Macaca radiata) zona pellucida-1 and zona pellucida-3 glycoproteins to inhibit in vitro human sperm-egg binding. 1562 95


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