UMLS:C0002453 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002453 (amenorrhea)
6,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pregnancy-associated plasma protein-A (PAPP-A) is a recently described glycoprotein of unknown biological function. The development of a radioimmunoassay enabled us to measure plasma levels of PAPP-A and human chorionic gonadotrophin (hCG) in 12 non-pregnant volunteers and in 159 women in early pregnancy attending the outpatient clinic for legal abortion. PAPP-A but not hCG was measurable in all non-pregnant women. In pregnant patients (with 36 to 86 days of amenorrhea) hCG reached a peak value (163.1-197.6 ng/ml) between the 9th and the 13th week whereas PAPP-A steadily increased throughout this period of pregnancy. Between the 6th and the 13th week after the last menstrual period, levels of PAPP-A increased proportionally more than hCG. This work provides the first evidence of a PAPP-A production in non-pregnant subjects and the very early marked increase of PAPP-A secretion during pregnancy.
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PMID:Pregnancy-associated plasma protein-A (PAPP-A) and hCG in early pregnancy. 616 64

A vaccine for pregnancy prevention made of purified beta-subunit of human chorionic gonadotropin (hCG) covalently linked to tetanous toxoid was tested in 15 healthy women who had previously undergone tubal ligation. The objectives of the trial described were to 1) evaluate the magnitude, constancy, and duration of the antibody response; 2) to determine whether immunization gave any evidence of toxicity or unwanted side reactions; 3) to determine whether the antibodies neutralized the biologic activity of hCG in vitro and in vivo test systems; and 4) to examine the cross-reactions between the antibodies and other glycoprotein hormones. This was a multicentered clinical trial with 1 clinic each in Sweden, Finland, Chile, and Brazil participating. 14 of 15 women had antibodies detectable by radioimmunoassay, the longest response lasting 400 days after injection. Duration of response to hCG antibody varied among participants. Clinical and immunological, hematological, and biochemical surveillance of the study participants lasted over 2 years, and during that time no significant signs of local or systemic intolerance to the vaccine were noted. Menstrual and endocrine changes were evaluated, and, aside from 1 case of 120-day amenorrhea postinjection, menstrual and endocrine changes were judged insignificant or unrelated to the vaccine. Body weight increase was the single greatest complaint among the women involved, followed by breast and andexal tenderness, and in a few cases colostrum development. In vitro, antisera were capable of neutralizing the activity of hCG in stimulating testosterone production in Leydig cell cultures.
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PMID:Observations on the antigenicity and clinical effects of a candidate antipregnancy vaccine: beta-subunit of human chorionic gonadotropin linked to tetanus toxoid. 741 85

Female bonnet monkeys Macaca radiata (n = 8, four per group) were immunized with purified 55 kDa glycoprotein from porcine zona pellucida (ZP3) and ZP3 conjugated to the beta subunit of human chorionic gonadotrophin (beta hCG) using adjuvants permissible for human use (alum, muramyl dipeptide and sodium phthalyl derivative of lipopolysaccharide). The animals were monitored for anti-ZP3 antibody titres, biweekly progesterone concentrations, menstrual cyclicity and status of fertility. All the animals generated a good anti-ZP3 antibody response, continued to have ovulatory cycles, remained infertile in the presence of high anti-ZP3 antibody titres and showed no disturbance in cyclicity (except summer amenorrhoea). Examinations by laparoscope showed normal ovaries with developing follicles or corpora lutea on the surface. Fifty per cent of the animals conceived after a decline in antibody titres. Ovaries of animals that failed to regain fertility were examined for changes in morphology at times when anti-ZP3 antibody titres in the circulation were low and following a booster when titres were high. None of the ovaries showed any sign of inflammation or lymphocytic infiltration. Follicles at different stages of development were seen in all of the ovaries. No significant reduction in the number of follicles, except in one monkey (MRA 178), was observed. There was no increase in the numbers of atretic or degenerating follicles. The results showed that ZP3 immunization with permissible adjuvants could be used for immunocontraception without obvious ovarian changes.
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PMID:Antifertility effects of porcine zona pellucida-3 immunization using permissible adjuvants in female bonnet monkeys (Macaca radiata): reversibility, effect on follicular development and hormonal profiles. 752 78

To investigate the relevance of glycoprotein polymorphism to gonadotropin bioactivity in vivo, plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH), 17 beta-estradiol (E2), testosterone and sex hormone binding globulin (SHBG) levels in 17 amenorrheic women affected with anorexia nervosa (14-29 years) and 10 age-matched normally cycling women were evaluated. Plasma FSH and LH levels were assayed using radioimmunoassay (RIA) and immunoradiometric assay (IRMA) methods, before and after concanavalin A-Sepharose (Con A) affinity chromatography. Significant RIA-IRMA differences in FSH and LH plasma values were present only in women with anorexia nervosa (p < 0.005). Moreover, in these patients both FSH and LH showed a reduced binding to the Con A, expressed as a percentage of unbound, suggesting altered glycosylation of these moieties. In conclusion, these findings hypothesize the involvement of glycosylation polymorphism in RIA-IRMA differences; support the usefulness of both RIA and IRMA methods in FSH and LH evaluation, before and after Con A chromatography; and suggest a new pathogenetic pathway to explain amenorrhea in anorexia nervosa.
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PMID:Altered glycosylation of pituitary gonadotropins in anorexia nervosa: an alternative explanation for amenorrhea. 771 83

Previous studies have demonstrated the efficacy, in mice, of synthetic peptides derived from zona pellucida (ZP) glycoprotein in blocking fertility without ovarian dysfunction. This study used bonnet monkeys (closely related to humans in the primate evolutionary tree and less susceptible to summer amenorrhea than rhesus monkeys) to explore the design of an immunocontraceptive vaccine based on synthetic peptides, recombinant glycoproteins, or proteins corresponding to ZP. Immunization of female monkeys with pig ZP3 glycoprotein using adjuvants permissible for human use produced infertility. Although only half the animals conceived after antibody titres declined, monkeys that failed to conceive did not show any obvious ovarian changes. Mapping of the epitopes recognized by monoclonal antibodies against ZP3 alpha and beta and possessing contraceptive efficacy in vitro identified an N-blocked decapeptide from the N-terminus corresponding to 23-32 amino acids of the precursor protein of pig ZP3 beta. When DNA encoding bonnet monkey ZP3 was cloned and sequenced, the deduced primary amino acid sequence showed a 93.9% similarity with human ZP3. Bonnet monkey ZP3 corresponding to an internal 975 nucleotide fragment excluding the N-terminus signal sequence and the C-terminus transmembrane domain has been expressed in Escherichia coli.
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PMID:Strategies for designing an immunocontraceptive vaccine based on zona pellucida synthetic peptides and recombinant antigen. 898 75

The goals of this study were to determine whether women with idiopathic hypogonadotropic hypogonadism (IHH) respond to pulsatile GnRH replacement therapy with exaggerated glycoprotein free alpha-subunit (FAS) levels, as reported in GnRH-deficient men, and to determine whether this pattern is unique to congenital GnRH deficiency or is also characteristic of patients with hypogonadotropic hypogonadism caused by other factors. GnRH was administered i.v. at a physiologic frequency and dose (75-100 ng/kg.bolus) to women with IHH (n = 11; n = 6 with anosmia); acquired GnRH deficiency secondary to treatment for cranial tumors (AHH; n = 7); and secondary hypothalamic amenorrhea (HA; n = 8). Results were compared with 24 normal cycling women. Gonadotropins, sex steroids, and FAS levels were measured in samples drawn daily across induced or normal menstrual cycles in patients or normal women, respectively. Samples were drawn at the same time of day and were collected 45 min after a GnRH bolus in patients. All women ovulated in response to pulsatile GnRH. There were no differences in the patterns of LH or gonadal steroid secretion between any of the patient groups (IHH, AHH, and HA). The patterns of LH and FSH secretion in the induced patient cycles were not different from normal women, with the exception of lower midcycle FSH levels in IHH women (P < 0.002). However, the daily dynamic secretion of FAS was exaggerated in IHH (compared with AHH, HA, and normal) women (P < 0.002). The increase in FAS levels in IHH was dependent on cycle stage, with the greatest difference observed during the early (P < 0.005) and midfollicular phase (P < 0.05) and the early luteal phase (P < 0.05). There was no difference in FAS between groups during the late follicular phase, at the midcycle, or in the midluteal and late luteal phase. This exaggerated FAS response to GnRH replacement in IHH was demonstrated in repeat cycles in two patients. Conclusions are: 1) Women with IHH respond to pulsatile GnRH replacement with an exaggerated secretion of FAS, which seems to be modified by gonadal factors; 2) this exaggerated FAS response, which is similar to that seen in GnRH-deficient men, is unique to congenital GnRH deficiency, and it is not observed in patients with acquired or secondary hypogonadotropic hypogonadism, suggesting that IHH patients may be missing a factor, in addition to GnRH, which normally restrains FAS secretion; and 3) the FAS response may prove to be a useful marker to distinguish constitutional delay of puberty from congenital GnRH deficiency.
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PMID:Exaggerated free alpha-subunit levels during pulsatile gonadotropin-releasing hormone replacement in women with idiopathic hypogonadotropic hypogonadism. 943 49

In order to evaluate the immunocontraceptive potential of zona pellucida (ZP) glycoproteins, recombinant bonnet monkey (Macaca radiata) zona pellucida glycoprotein-1 (r-bmZP1) and -2 (r-bmZP2) were expressed as polyhistidine fusion proteins in Escherichia coli. Female bonnet monkeys were immunized with the purified r-bmZP1 (n=5) and r-bmZP2 (n=4) conjugated to diphtheria toxoid (DT). Immunization led to generation of antibodies against r-bmZP1, r-bmZP2 and DT as determined by enzyme linked immunosorbent assay. The immunized animals exhibited normal menstrual cyclicity and progesterone profile, except during the summer amenorrhoea. Immunized animals, when mated with males of proven fertility, showed protection from conceiving for cumulative 45 ovulatory cycles in r-bmZP1-DT immunized group and 32 ovulatory cycles in r-bmZP2-DT immunized group. Ovarian histopathology of both the immunized groups revealed the presence of atretic follicles with degenerated oocytes, which may have been the principle cause for the failure of immunized animals to conceive in spite of the decline in either anti-r-bmZP1 or anti-r-bmZP2 antibody titres to background levels. These studies demonstrate, for the first time, that the block of fertility subsequent to immunization with r-bmZP1 and r-bmZP2, in a homologous non-human primate model, may be mediated due to ovarian dysfunction.
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PMID:Evaluation of the immunocontraceptive potential of Escherichia coli expressed recombinant non-human primate zona pellucida glycoproteins in homologous animal model. 1244 65

Zona pellucida (ZP) glycoproteins have been proposed as candidate antigens for development of immunocontraceptive vaccines. In this study, the efficacy to block fertility by immunization with recombinant bonnet monkey (Macaca radiata) zona pellucida glycoprotein-C (r-bmZPC) expressed in Escherichia coli and its synthetic peptide (P(4): KGDCGTPSHSRRQPHVVSQWSRSA, aa residues 324-347) conjugated to diphtheria toxoid (DT) has been evaluated in a homologous system. Female bonnet monkeys, immunized with P(4)-DT conjugate showed better immunocontraceptive potential as compared to an r-bmZPC-DT immunized group. In spite of high anti-P(4) antibody titres, animals continued to have ovulatory cycles and showed no disturbance in cyclicity (except summer amenorrhoea). No ovarian pathology was observed in the P(4) immunized group. These results suggest that immunization with the P(4) may lead to block in fertility without obvious ovarian dysfunction. However, further inputs are required to identify additional ZP based B-cell epitopes to enhance the contraceptive efficacy.
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PMID:Immunocontraceptive potential of recombinant bonnet monkey (Macaca radiata) zona pellucida glycoprotein-C expressed in Escherichia coli and its corresponding synthetic peptide. 1253 23

The acquisition of a sexually dimorphic phenotype is a critical event in mammalian development. Hypogonadotropic hypogonadism (HH) results from impaired secretion of GnRH. The patients display with delayed puberty, micropenis and cryptorchidism in the male reflecting gonadotropin insufficiency, and amenorrhea in the female. Kallmann's syndrome (KS) is defined by the association of HH and anosmia or hyposmia (absent smelling sense). Segregation analysis in familial cases has demonstrated diverse inheritance patterns, suggesting the existence of several genes regulating GnRH secretion. The X-linked form of the disease was associated with a genetic defect in the KALI gene located on the Xp22.3 region. KAL1 gene encodes an extracellular matrix glycoprotein anosmin-1, which facilitates neuronal growth and migration. Abnormalities in the migratory processes of the GnRH neurons with the olfactory neurons explain the association of HH with anosmia. Recently, mutations in the FGF recepteur 1 (FGFR1) gene were found in KS with autosomal dominant mode of inheritance. The role of FGFR1 in the function of reproduction requires further investigation. Besides HH with anosmia, there are isolated HH (IHH). No human GnRH mutations have been reported although hypogonadal mice due to a GnRH gene deletion exist. In patients with idiopathic HH and without anosmia an increasing number of GnRH receptor (GnRHR) mutations have been described which represent about 50% of familial cases. The clinical features are highly variable and there is a good relationship between genotype and phenotype. A complete loss of function is associated with the most severe phenotype with resistance to pulsatile GnRH treatment, absence of puberty and cryptorchidism in the male. In contrast, milder loss of function mutations causes incomplete failure of pubertal development. The preponderant role of GnRH in the secretion of LH by the gonadotrophs explains the difference of the phenotype between male and female with partial GnRH resistance. Affected females can have spontaneous telarche and normal breast development while affected males exhibit no pubertal development but normal testis volume, a feature described as "fertile-eunuch". High-dose pulsatile GnRH has been used to induce ovulation. Another gene, called GPR54, responsible for idiopathic HH has been recently described by segregation analysis in two different consanguineous families. The GPR54 gene is an orphan receptor, and its putative ligand is the product of the KISS-1 gene, called metastine. Their roles in the function of reproduction are still unknown.
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PMID:[GnRH deficiency: new insights from genetics]. 1514 60

Anti-mullerian hormone (AMH) is a glycoprotein produced by granulosa cells of primary, pre-antral and small antral ovarian follicles and its clinical applicability has been recently demonstrated by several studies. Prediction of the response to ovarian stimulation for in vitro fertilization corresponds to the most frequent utilization of AMH in clinical practice, being routinely assessed in many services to identify subgroups of women susceptible to a poor response or to Ovarian Hyperstimulation Syndrome. There are great perspectives that AMH may be applicable to the individual determination of risk for iatrogenic gonadal injury in women with neoplasms who will be submitted to chemotherapy. It is also probable that AMH assessment will be included in protocols for the investigation of amenorrhea and oligomenorrhea, since AMH levels are increased in Polycystic Ovary Syndrome, reduced in premature ovarian failure and normal in other conditions such as hyperprolactinemia and hypogonadotropic hypogonadism. It is possible that AMH will be utilized in the future for the prediction of age at menopause and of reproductive prognosis, providing solid bases for pre-conceptive and contraceptive counseling.
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PMID:[Clinical use for anti-mullerian hormone in gynecology]. 2353 73

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