Dietary phytoestrogens dampen female sexual behavior in mice with a disrupted aromatase enzyme gene.

Aromatization of testosterone (T) to estradiol (E2) during perinatal development in male rodents plays a significant role in sexual differentiation of the brain and adult behaviors. Exposure to estrogens during development can enhance masculine behaviors in adult females and reduce expression of female-typical behaviors in adult males. Previous studies have shown that, in addition to naturally occurring estrogens, dietary phytoestrogens can affect sexual differentiation. To distinguish between the effects of endogenous T-derived E2 and exogenous phytoestrogens, the authors used an aromatase knockout (ArKO) mouse that cannot produce E2 but is responsive to E2 via estrogen receptors α and β. Dams and their litters were maintained either on a standard mouse chow that was rich in phytoestrogens or on a chow nearly devoid of phytoestrogens. Mice were maintained on their perinatal diets after weaning. Adults of both sexes were gonadectomized and tested for lordosis behavior. In the ArKO females raised on a diet high in phytoestrogens, lordosis was reduced in comparison with females of both genotypes on the low phytoestrogen diet. The authors' findings suggest that dietary phytoestrogen consumption may partially defeminize adult female sexual behavior in the mouse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Definition and significance of polycystic ovaries

Defining the polycystic ovarian syndrome (PCOS) has challenged clinicians for many years. The clinical, hormonal and morphological definitions of PCOS have their own limitations and do not correspond exactly. Clinically, PCOS can be schematically divided into three components, i.e. hyperandrogenic, anovulatory and dysmetabolic. No one is specific for the syndrome. Hormonally, PCOS has recently been defined by the GnRH agonist test as a functional abnormality in ovarian androgen synthesis. This functional ovarian hyperandrogenism seems closely linked to hyperinsulinism secondary to an insulin resistance. Morphologically, ovarian ultrasonography has emerged in the last decade or so as a new diagnostic tool. However, the sonographic definition of the polycystic ovary (PCO) is controversial, mainly because of a lack of consensus about normative data. The aim of this review is to present the diagnostic dilemma in the diagnosis of PCOS and to discuss the prognostic significance of the PCO.     

Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews

PURPOSE: To measure binocular function and patient satisfaction with monovision induced by photorefractive keratectomy (PRK) in myopic presbyopic patients. SETTING: Refractive Department, Cleveland Clinic, Cleveland, Ohio, USA. METHODS: This study comprised 21 myopic presbyopic patients with monovision induced by PRK. Sixteen emmetropic patients who had PRK served as a control group. Monovision was induced by undercorrecting the nondominant eye by 1.25 diopters for near vision and correcting the dominant eye with emmetropia for distance vision. Monocular and binocular uncorrected Snellen visual acuities at 20 feet and 13 inches, manifest refraction, ocular dominance, stereopsis at 20 feet and 13 inches, monocular and binocular contrast sensitivities, Worth-4-Dot test at 20 feet and 1/3 of a meter, and fusional convergence amplitudes were examined in each patient. RESULTS: In the monovision group at near and distance, 20 patients (95.3%) had binocular visual acuity of 20/25 or better. No patient in the monovision group used reading glasses postoperatively; 4 of 16 patients (25.0%) in the control group used such glasses. All patients maintained binocular fusion and stereo acuity ranging from 40 to 800 seconds of arc. Mean patient satisfaction was 86% (range 40% to 100%). In the control group, 12 patients (75.0%) had binocular distance visual acuity of 20/25 or better and 11 (68.8%) had binocular near visual acuity of 20/25 or better. CONCLUSION: Monovision PRK patients had better near vision than control PRK patients, with minimal compromise in stereo acuity and overall high patient satisfaction.     

Molecular basis of human complement C1s deficiency

This is the first report on the molecular basis of human complement C1s deficiency. Two abnormalities in the C1s gene were identified in a Japanese family, including one patient, by using exon-specific PCR, single-strand conformation polymorphism analysis, and nucleotide sequencing. A deletion of 4 bp, TTTG, was identified in exon X when using genomic DNA from the patient, his father, and his paternal grandmother. They were all heterozygous for the mutation. The mutant gene encodes a truncated C1s from the N terminus to the short consensus repeat domain. By further sequencing the PCR products, a nonsense mutation from G to T was identified at codon 608 in exon XII in the patient, his mother, and his sister. They were all heterozygous for the nonsense mutation. The mutant gene encodes a truncated form of C1s that lacks the C-terminal 80 amino acids. These results indicate that the patient was a compound heterozygote with the 4-bp deletion on the paternal allele and the nonsense mutation on the maternal allele. The levels of serum C1s seem to be correlated to the genotypes of the C1s gene in which no C1s was detected in the patient, and one-half of the normal level in the family members who are heterozygous for either mutation. The present study demonstrates that the disease is inherited in an autosomal recessive mode.     

Reproductive ability of an adult female with Silver-Russell syndrome

An adult female with typical features of Silver-Russell dwarfism gave birth to a viable infant. Despite the abnormalities in sexual development that may be associated with the Silver-Russell syndrome, fertility is not necessarily impaired, at least in females. The growth and development of children with the Silver-Russell syndrome have been studied (Silver, 1964; Tanner et al., 1975). There is, however, virtually no information available about adult patients with this syndrome. It is known that both male and female Silver-Russell dwarfs develop secondary sexual characteristics (Rimoin, 1969; McDowell and Sproles, 1973) but fertility of these patients has not been described previously.     

Neonatal androgenic stimulation and adult sexual behavior in male and female golden hamsters.

In an experiment with 48 male and 48 female golden hamsters, neonatally and adult castrated males as well as neonatally androgenized and nonandrogenized females were tested for both mounting and lordosis behaviors during treatment with either testosterone or ovarian hormones. Neonatal androgenization facilitated mounting behavior in adult Ss administered either testosterone or ovarian hormones and suppressed lordosis behavior in adult ovarian-hormone-treated Ss. Early androgen effects on the display of lordosis behavior during adult testosterone treatment were complex and varied with the exact timing of perinatal endogenous or exogenous androgenization. Species differences in hormone-behavior relationships and the possible role of perinatal androgenization in the development of rodents' ability to aromatize androgens are discussed. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom)

We report the features of a new syndrome of aromatase deficiency due to molecular defects in the CYP19 (P450arom) gene in a 46,XX female. At birth, the patient presented with a nonadrenal form of female pseudohermaphrodism. At 17 months of age, laparotomy revealed normal female internal genital structures; the histological appearance of the ovaries was normal. FSH concentrations were markedly elevated at 9.4 ng/mL LER 869, and estrone and estradiol levels were undetectable (< 37 pmol/L). By 14 yr of age, she had failed to exhibit breast development. The clitoris had enlarged to 4 x 2 cm, and pubic hair was Tanner stage IV. The plasma concentration of testosterone was elevated at 3294 pmol/L, as was androstenedione at 9951 pmol/L. Plasma estradiol levels were below 37 pmol/L. ACTH and dexamethasone tests indicated a nonadrenal source of testosterone and androstenedione. Plasma gonadotropin levels were in the castrate range. Pelvic sonography and magnetic resonance imaging showed multiple 4- to 6-cm ovarian cysts bilaterally. Despite increased circulating androgens and clitoral growth, the bone age was 10 yr at chronologic age 14 2/12 yr. Estrogen replacement therapy resulted in a growth spurt, breast development, menarche, suppression of gonadotropin levels, and resolution of the cysts. The clinical findings suggested the diagnosis of P450arom deficiency. Analyses of genomic DNA from ovarian fibroblasts demonstrated two single base changes in the coding region of the P450arom gene, one at 1303 basepairs (C-T), R435C, and the other at 1310 basepairs (G-A), C437Y, in exon 10. The molecular genetic studies indicate that the patient is a compound heterozygote for these mutations. Expression of these mutations showed that the R435C mutation had 1.1% the activity of the wild-type P450arom enzyme, whereas the C437Y mutation demonstrated no activity. The cardinal features of this syndrome are a consequence of P450arom deficiency: 1) the fetal masculinization in this syndrome can be ascribed to defective placental conversion of C19 steroids to estrogens, leading to exposure of the female fetus to excessive amounts of testosterone; 2) the pubertal failure, mild virilization, multicystic ovaries, and hyperstimulation of the ovaries by FSH and LH are the result of the inability of the ovary to aromatize testosterone and androstenedione to estrogens; and 3) the striking delay in bone age at 14 2/12 yr supports the notion that estrogens, in contrast to androgens, are the major sex steroid driving skeletal maturation during puberty. Familial P450arom deficiency, although rare, may be more common than previously suspected.(ABSTRACT TRUNCATED AT 400 WORDS)     

Normal development and metabolic activity of preimplantation embryos in vitro from patients with polycystic ovaries

Polycystic ovary syndrome (PCOS) is closely associated with high miscarriage rates and, following in-vitro fertilization (IVF), with decreased fertilization rates, suggesting that oocytes and embryos are of poor quality. In this prospective study, we examined the development, metabolic activity and blastocyst cell number of embryos following IVF from 51 patients with either anovulatory PCOS, ovulatory PCOS or tubal disease. The number of oocytes retrieved and the fertilization rates were similar for patients with PCOS and tubal disease. Following embryo transfer, 46% of the patients with PCOS and 36% of patients with tubal disease became pregnant. A similar proportion of surplus embryos from patients with PCOS and tubal disease developed to the blastocyst stage (38% and 43% respectively). Patients with anovulatory PCOS had embryos with less fragmentation which cleaved faster, cavitated earlier and had more cells at the blastocyst stage than embryos from patients with tubal disease. While the profile of glucose uptake and lactate production was similar for all groups throughout preimplantation development, patients with tubal disease who underwent ovulation induction using the 'titrated' regimen optimized for PCOS patients resulted in embryos with reduced pyruvate uptake, in addition to low blastocyst cell numbers. This study demonstrates that with an optimized ovulation induction regimen, embryos from PCOS patients are of good quality and developmental potential.     

The role of insulin-like growth-factor binding proteins in normal and polycystic ovaries

The insulin-like growth factor binding proteins are single chain polypeptides, that can bind insulin-like growth factors, but not insulin. They can serve as autocrine or paracrine regulators of the actions of insulin-like growth factor. The human granulosa cells produce insulin-like growth factor-II but not insulin-like growth factor-I, while the human theca cells produce insulin-like growth factor-I and II. Polycystic ovarian syndrome is a disorder which is characterised by hyperandrogenism and anovulation. In polycystic ovarian syndrome there is a disorder of follicular development, with the accumulation of antral follicles within the ovary which fail to respond appropriately to endogenous follicle-stimulating hormone. Significance is given to insulin-like growth factor binding proteins, which have an inhibitory action on follicle-stimulating hormone. No differences were found in the total level of insulin-like growth factor binding proteins follicular profiles between women with polycystic ovarian syndrome and without it. Serum insulin-like growth factor binding protein-I levels are lower in polycystic ovarian syndrome with hyperinsulinaemia, probably as a consequence of insulin-mediated suppression of insulin-like growth factor binding protein-I. Consequently, serum free insulin-like growth factor-I levels are higher. This alteration may cause an excessive thecal androgen production. The alterations in the insulin-like growth factor-insulin-like growth factor binding proteins axis may be one of several mechanisms that help to sustain the steady state of anovulation and follicular dysmaturation that are characteristic of this syndrome.     

Ultrasonographic patterns of polycystic ovaries: color Doppler and hormonal correlations

Ultrasound has been used in the identification of two different morphological patterns of polycystic ovaries, namely a peripheral cystic pattern and a general cystic pattern. The aim of this study was to evaluate whether patients with the peripheral form of polycystic ovaries showed different ovarian and uterine blood flow from those with the general form, and to investigate whether there was a correlation between the forms and different hormonal parameters. Eighteen patients with the general form and 16 patients with the peripheral form of polycystic ovary underwent clinical, biochemical, gray-scale and color Doppler ultrasonographic evaluation. The parameters analyzed confirmed polycystic ovarian syndrome (PCOS) in all patients. Individual levels of plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, androstenedione and estradiol did not differ between the groups. However, there was a significantly higher LH/FSH ratio and a greater stromal echodensity in the peripheral cystic group than in the general cystic group. Doppler ultrasonography demonstrated significantly lower pulsatility index values in the intraovarian arteries of the peripheral cystic group and a higher rate of visualization of these arteries than in the general cystic group. These findings suggest that, apart from the LH/FSH ratio, the different morphological types of polycystic ovary do not reflect differences in endocrine profile. The differences in blood flow demonstrated by Doppler assessment in each case, however, showed that PCOS does not predetermine a single intraovarian blood flow pattern.     

The Williams-Campbell syndrome diagnosed in an adult female patient

This article outlines the planning and setting up of an advice and discussion group for people with osteoporosis and their families to give a fuller understanding of the condition and how to manage it.     

Splenic-gonadal fusion of the continuous type in an adult female

The use of autogenous fat for augmentation of the paralyzed vocal fold is a promising substitute for alternate injectable material such as Teflon (polytef paste, polytetrafluoroethylene; Ethicon) and Gelfoam (absorbable gelatin sponge; Upjohn). Long-term histologic evaluation of fat grafts to the larynx has not previously been reported in the literature. We present a case report of autogenous fat augmentation of a paralyzed vocal fold with documentation of persistent fat graft present 5 months after transplant.     

Consequences of perinatal hormone manipulation on the adult sexual behavior of female rats.

Compared male and female behavior of 46 female Sprague-Dawley albino rats treated with prenatal or prolonged postnatal testosterone propionate (TP) or cyproterone acetate (Cyp A), an antiandrogen, to 13 control females. Prenatal TP decreased quality and rate of lordotic responding while increasing incomplete and complete male copulatory rate. Postnatal TP also impaired female behavior but increased only complete male copulations. Results suggest that, in the rat, gonadal steroid levels present during prenatal as well as postnatal developmental stages determine the direction and degree of differentiation of adult sexual behavior. Prenatal Cyp A had no effect on female behavior or external genitalia but decreased both types of male copulatory responses, suggesting that male behavior in normal females is based on prenatal androgenic modification of the nervous system. (30 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Posttraumatic stress disorder in adult female survivors of child sexual abuse: A comparison study.

This study compared symptoms of posttraumatic stress disorder (PTSD) in a group of 45 adult women in outpatient treatment for childhood sexual abuse (CSA) and a group of 31 women who reported no CSA. The comparison group consisted of women in outpatient treatment for problems in their committed relationships with male living partners. This research also investigated the traumatic impact of dual abuse (both childhood sexual and physical abuse). Standardized assessment instruments were used to measure PTSD, CSA, and childhood physical abuse (CPA). Results indicated that 86.7% of the CSA group met criteria for current PTSD in accordance with the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised; American Psychiatric Association, 1987), compared with 19.4% of the relationship distress group, providing support for CSA as an etiological agent for PTSD. In addition, 89% of the CSA survivors reported CPA. Multivariate analysis revealed that both CSA and CPA exposure variables accounted for a significant portion of the variance in PTSD symptoms in the CSA group. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Further evidence of increased aromatase activity in granulosa luteal cells from polycystic ovary

This study evaluated the effect of atamestane (a competitive inhibitor of P-450 aromatase) on granulosa luteal cells from polycystic and normal ovaries. Treatment with atamestane (10 micromol/l) determined a strong inhibition of basal aromatase activity in both types of cells; however, its effect was markedly more pronounced in granulosa cells from normal ovary than in granulosa cells from polycystic ovaries (PCO; P < 0.01). Concomitant treatment with insulin (25 microg/ml) and increasing doses of atamestane (0.01-10 micromol/l) caused a dose-dependent inhibition of insulin-stimulated aromatase activity, but again with marked differences between the two types of cells. In granulosa cells from PCO, the minimal effective dose of atamestane was 1 micromol/l and it had an EC50 of 2.23 +/- 0.4 micromol/l and a maximal inhibitory effect of 75%; in granulosa cells from normal ovary, the minimal effective dose of atamestane was 0.01 micromol/l, the EC50 was 0.4 +/- 0.07 micromol/l, and the maximal inhibitory effect was 94%. Significant differences were observed between the different cells at all the studied dose points. Reversibility studies showed that resumption of aromatase activity in granulosa cells from PCO is basally greater and more inducible with insulin treatment. This study provides further evidence of an increased in-vitro function of the aromatase complex in granulosa cells from PCO, that could be induced by an altered cellular autoregulation.