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)

Twenty-eight X-linked, recessive mutations of Drosophila melanogaster conferring enhanced sensitivity to the monofunctional alkylating agent, methyl methanesulfonate, have been recoered and assigned to five complementation groups. These groups can be distinguished on the basis of map location and variations in the pattern of mutagen sensitivity. Allelism of members of one complementation group with the previously described meiotic mutant, mei-41, (Baker and Carpenter, 1972) as well as the frequent appearance of female infertility with mutagen sensitivity suggests associated defects in meiotic chromosome behavior or early embryogenesis. Examination of the mutagen sensitivity of double mutants has led to the formulation of a working model of DNA repair for this organism. Studies of a similar nature (Boyd et al., 1976) have identified five additional X chromosome complementation groups, suggesting that the genome of Drosophila melanogaster may contain many loci involved with mutagen sensitivity. The continued isolation and characterization of conditional mutants of this type promises future insights into the mechanisms of DNA replication, DNA repair and recombination in this complex higher eucaryote.
Mol Gen Genet 1976 Nov 24
PMID:Mutagen sensitivity of Drosophila melanogaster. III. X-linked loci governing sensitivity to methyl methanesulfonate. 18 78

GnRH plays a pivotal role in the reproductive system, and GnRH analogs have wide therapeutic applications ranging from the treatment of prostatic cancer to infertility. Determination of the predicted structure of the GnRH receptor (GnRHR) would illuminate the mechanisms of receptor activation and regulation and allow directed design of improved GnRH analogs. We report the cloning of a cDNA representing the mouse GnRHR and confirm its identity using Xenopus oocyte expression. Injection of sense RNA transcript leads to the expression of a functional, high affinity GnRHR. Expression of the GnRHR using gonadotrope cell line RNA, however, is blocked by an antisense oligonucleotide. In situ hybridization in the rat anterior pituitary reveals a characteristic GnRHR distribution. The nucleotide sequence encodes a 327-amino acid protein which has the seven putative transmembrane domains characteristic of G protein-coupled receptors, but which lacks a typical intracellular C-terminus. The unusual structure and novel potential regulatory domain of the GnRHR may explain unique aspects of its signal transduction and regulation.
Mol Endocrinol 1992 Jul
PMID:Cloning and functional expression of a mouse gonadotropin-releasing hormone receptor. 132 22

The sera of vasectomized men and of patients with immune infertility were used to study the antigens and epitopes of sperm nuclear proteins that bind antibodies in these sera. No reaction with sperm histones was observed except for one serum. P1, P2 protamines and pro-P2 protamines were recognized by auto-antibodies. Studies with peptides derived from P1 and P2 protamines and with mammalian protamines related to HP1 showed that antibodies are mainly specific for a folded protamine molecule, more especially antibodies from vasectomized men. These results disagree with the random coil model proposed for protamines by several previous works. A cross-reactivity between P1 and P2 protamines was observed only for the whole molecules and not for peptides derived from them. This observation suggests that the two classes of protamines, different in sequence, may have a similar folding and thereby may be functionally equivalent.
Mol Immunol
PMID:Auto-antibodies to human sperm basic nuclear proteins in infertile and vasectomized men: characterization of antigens and epitopes recognized by antibodies. 137 33

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

A study was conducted to compare results between culture methods and the Gen-Probe (Gen-Probe Inc. San Diego, California) chemiluminescent technique of nucleic acid hybridization to identify Chlamydia trachomatis from genital specimens from 117 females and 70 males. Specimens collected from sexually transmitted diseases (STD) and infertility clinics were randomized as to whether probe or culture swabs were collected first. The Gen-Probe demonstrated a sensitivity of 83% and a specificity of 75% in the female population and a sensitivity of 68% and a specificity of 75% in the male population when compared to the reference culture method using cycloheximide-treated McCoy cells. Gen-Probe had an overall sensitivity of 74% and specificity of 75% when the two groups were combined. Chlamydiazyme (Abbott Labs) results were obtained on 135 specimens; 90 of which correlated with probe and culture. The remaining 45 specimens had varying combinations of probe, culture and Chlamydiazyme results. MicroTrak (Syva) was done on 49 specimens; 35 of which correlated with probe and culture. The remaining 14 specimens had varying combinations of probe, culture and MicroTrak results. The apparent lack of sensitivity of the DNA probe is a major drawback of this system.
Mol Cell Probes 1990 Feb
PMID:Comparison of a DNA probe with culture for detecting Chlamydia trachomatis directly from genital specimens. 217 11

A survey of the research on gossypol, the lipophilic agent derived from cotton seed already being used as male oral contraceptive in China and Brazil, leaves many questions unanswered as to its mode of action and safety. Gossypol is a polyphenolic dialdehyde, occurring in 2 racemic isomers with different biological activities. It is soluble in lipids, binds to membranes, inhibits several enzymes including arachidonate lipoxygenases, and is an antioxidant. It has been used traditionally to treat bronchitis and to induce abortion and menses, but was only recognized as a male antifertility agent in the 1970s. It is spermicidal, it inhibits sperm motility, and causes azoospermia, at different doses and with marked species variability. There is evidence from China for regional variation in effect, possibly related to genetic factors, or even more likely due to dietary intake. Whether infertility induced by gossypol is reversible is in dispute. The most common toxic side effect is hypokalemia, which is severe enough to cause temporary paralysis in 1% of 8806 volunteers in a study conducted in China. Whether potassium loss can be reversed by supplementation, or by taking potassium-sparing diuretics, has been questioned. Similarly, the extent and permanence of renal damage presumed responsible for potassium loss is uncertain. A suitable animal model for studies on gossypol, either in vivo or in vitro, is unavailable. Studies on the mechanism of action of gossypol suggest structural alterations of cell membranes, inhibition of enzymes and energy metabolism may be affected, but this type of work needs to be refined to pinpoint the site of action.
Mol Reprod Dev 1990 Apr
PMID:Effects of gossypol on the motility of mammalian sperm. 218 32

We have analyzed a line of transgenic mice derived from injection of a cloned human interferon cDNA. This line manifests total male sterility of males carrying the human sequence, while male littermates not harboring the foreign DNA are fertile. All females are fertile. Karyotypes of transgenic animals show 2:12 translocation. The microinjected sequence maps to one of the translocation chromosomes composed of a large portion of chromosome 12 to which has been translocated a segment of chromosome 2. Analysis of the sterile males reveals significant abnormalities of spermatogenesis and faulty chromosome synapsis that involves the translocation chromosomes. These findings show that transfer of foreign DNA into mouse embryos may lead to chromatin breakage and infertility of transgenic animals.
Somat Cell Mol Genet 1989 Nov
PMID:Association of foreign DNA sequence with male sterility and translocation in a line of transgenic mice. 259 56

The effect of PMHI on the epididymis and accessory sex glands (ventral prostate, seminal vesicle, and coagulating gland) was studied in a wild rodent, the bandicoot rat. Animals were given a single subcutaneous injection of PMHI (150 mg/kg body wt) and were killed 2, 10, or 30 days later. Treatment of PMHI resulted in severe alterations in the epididymis of the bandicoot rat with no apparent effect on accessory sex glands except for a transitory decrease in epithelial height of the seminal vesicle and in peripheral acini of the ventral prostate. Changes in the epididymis included a marked involution of the caput, Zone I in particular, formation of sperm granulomata, and the distension of the "clear" cells in the caudal portion of the duct. Sperms progressively disappeared from the lumen and by Day 30, the cauda epididymis became completely azoospermic. It appears that the epididymal lesions produced by this compound may play a contributory role to induce infertility in the bandicoot rat.
Exp Mol Pathol 1986 Apr
PMID:Effect of DL-6-(N-alpha-pipecolinomethyl)-5-hydroxyindane maleate (PMHI) on the reproductive system of a wild rat, Bandicota bengalensis. II. Epididymis and accessory sex glands. 369 37

The present study was conducted to investigate the molecular identities, nature of interaction, and tyrosine phosphorylation activity of the sperm-zona pellucida binding proteins in humans. Sperm proteins belonging to four major molecular regions, namely 95, 63, 51, and 14-18 kDa, reacted with zona pellucida proteins in the Western blot and immunoprecipitation procedures. In these procedures, zona pellucida protein that reacted strongest with the sperm proteins belonged to the molecular region of 55 kDa (ZP3), besides weakly reacting proteins in the 110-kDa (ZP1/ZP2) and 14-18-kDa molecular regions. The major forces involved in the sperm-zona protein interactions were of hydrophobic and ionic in nature. Three (95, 51, and 14-18 kDa) of the four molecular regions of sperm proteins that bound to the zona pellucida proteins also seem to involve o-phospho-L-tyrosine residues in their interaction, and these proteins demonstrated the presence of phosphotyrosine residues, and the 51-kDa protein also showed autophosphorylating activity in the in vitro kinase assay. The sperm binding zona protein of 55 kDa also demonstrated autophosphorylating activity. Using specific monoclonal antibody to the well characterized sperm-specific glycoprotein, designated FA-1, and the competitive inhibition in the immunoprecipitation procedure, it was found that the 51 kDa protein is indeed FA-1 antigen. Besides elucidating the molecular nature of the sperm-zona interaction, these antigens will find application in the development of a multivalent contraceptive vaccine, and may also help in specific diagnosis and treatment of infertility mediated through defective gamete (sperm or oocyte) function.
Mol Reprod Dev 1994 Dec
PMID:Molecular identities of human sperm proteins that bind human zona pellucida: nature of sperm-zona interaction, tyrosine kinase activity, and involvement of FA-1. 753 65

Although sex steroids have long been known to influence serum concentrations of SHBG, it is now recognized that nutritional factors may be more important in the regulation of SHBG in women. Thus, SHBG concentrations are negatively correlated with body mass index (BMI) and, more particularly, to indices of central adiposity. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is associated with truncal obesity, hyperandrogenism and hyperinsulinaemia. There is evidence that insulin may be the humoral mediator of the weight-dependent changes in SHBG. Serum SHBG concentrations are inversely correlated with both fasting and glucose-stimulated insulin levels, and insulin has been shown to have a direct inhibitory effect on SHBG synthesis and secretion by hepatocytes in culture. However, the interrelationship of BMI, insulin and SHBG appears to be different in women with PCOS from that in normal subjects. The clinical importance of the weight-related suppression of SHBG is illustrated by the finding of a greater prevalence of hirsutism in obese women PCOS compared with their lean counterparts. Obese subjects with PCOS have similar total testosterone concentrations to lean PCO women but have lower SHBG and reciprocally higher free testosterone levels. Calorie restriction results in reduction of serum insulin followed by an increase in SHBG and a fall in free testosterone but an isocaloric, low-fat diet has no significant effect on SHBG concentrations. Weight reduction in obese, hyperandrogenaemic women with PCO is an important approach to the management of both anovulation and hirsutism.
J Steroid Biochem Mol Biol 1995 Jun
PMID:Sex hormone-binding globulin and female reproductive function. 762 5


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