A role for dendritic protein synthesis in hippocampal late LTP.

The late temporal component of long-term potentiation (LTP), a putative neural mechanism for information storage in the brain, is protein synthesis-dependent, but the site of obligatory protein synthesis is not known. Here we show that when the protein synthesis inhibitor emetine is applied locally to the apical dendritic field of CA1 pyramidal cells in the murine hippocampus, late LTP is impaired at apical but not at basal dendrites, and conversely when emetine is applied locally to basal dendrites, late LTP is impaired only at basal dendrites. Thus, local protein synthesis modulates the expression of tetanically induced late LTP at Schaffer-commissural synapses on CA1 pyramidal cells.

Abnormal uterine bleeding in adolescents.

Irregular bleeding is a common complaint of adolescents and is responsible for approximately 50% of gynecologic visits in that age group. Most abnormal bleeding in adolescents is caused by immaturity of the hypothalamic-pituitary-ovarian axis resulting in anovulation. Approximately 20% of adolescents have an underlying disorder requiring targeted diagnostic testing. A thorough history and physical examination and laboratory findings will often reveal the source of abnormal bleeding. Appropriate treatment is then directed to the underlying cause.

Effect of low-dose oral contraceptives on androgenic markers and acne.

Oral contraceptives (OC) suppress excess androgen production; however, different progestins in combination with low-dose estrogens produce divergent effects on sex hormone-binding globulin (SHBG) and testosterone that may influence clinical outcomes. This multicenter, open-label, randomized study compared biochemical androgen profiles and clinical outcomes associated with two OC containing the same amounts of ethinyl estradiol (EE, 20 micrograms) but different progestins, levonorgestrel (LNG, 100 micrograms), and norethindrone acetate (NETA, 1000 micrograms). Fifty-eight healthy women (18-28 years old) received three cycles of treatment with LNG/EE (n = 30) or NETA/EE (n = 28). The results showed that LNG reduced androgen levels in three compartments--adrenal, ovarian, and peripheral. NETA reduced only adrenal and peripheral androgens. Despite a 2.2-fold greater relative increase in SHBG with NETA than LNG, bioavailable testosterone (T) was reduced by the same amount with LNG and NETA. Both treatments improved acne and were well tolerated. Low-dose OC (EE, 20 micrograms) are effective in reducing circulating androgens and acne lesions without causing weight gain. Although LNG and NETA affected secondary markers differently, both OC formulations produced an equivalent decrease in bioavailable.

PIP: Oral contraceptives (OCs) suppress excess androgen production; however, different progestins in combination with low-dose estrogens produce divergent effects on sex hormone-binding globulin (SHBG) and testosterone that may influence clinical outcomes. This multicenter, open-label, randomized study compared biochemical androgen profiles and clinical outcomes associated with 2 OCs containing the same amounts of ethinyl estradiol (EE, 20 mcg) but different progestins, levonorgestrel (LNG, 100 mcg), and norethindrone acetate (NETA, 1000 mcg). 58 healthy women aged 18-28 years received 3 cycles of treatment with LNG/EE (n = 30) or NETA/EE (n = 28). The results showed that LNG reduced androgen levels in 3 compartments-adrenal, ovarian, and peripheral. NETA reduced only adrenal and peripheral androgens. Despite a 2.2-fold greater relative increase in SHBG with NETA than LNG, bioavailable testosterone (T) was reduced by the same amount with LNG and NETA. Both treatments improved acne and were well tolerated. Low-dose OC (EE, 20 mcg) are effective in reducing circulating androgens and acne lesions without causing weight gain. Although LNG and NETA affected secondary markers differently, both OC formulations produced an equivalent decrease in bioavailable T.

Juvenile granulosa cell tumor in a 13-year-old girl with enchondromatosis (Ollier's disease): a case report.

Juvenile granulosa cell tumor (JGCT) of the ovary has been reported to occur rarely in conjunction with Ollier's disease. We report a case of a 13-year-old girl who was noted to have a large abdominal mass at the time of excision of a symptomatic enchondroma of the right femur. Subsequent laparotomy at a tertiary care children's medical center identified a JGCT confined to the right ovary. Review of the literature reveals eight previous cases of JGCT in patients with Ollier's disease. The pathophysiology and possible common causes of both disorders is discussed.

Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3.

Defects in the conversion of androstenedione to testosterone in the fetal testes by the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) give rise to genetic males with female external genitalia. We have used expression cloning to isolate cDNAs encoding a microsomal 17 beta-HSD type 3 isozyme that shares 23% sequence identity with other 17 beta-HSD enzymes, uses NADPh as a cofactor, and is expressed predominantly in the testes. The 17 beta HSD3 gene on chromosome 9q22 contains 11 exons. Four substitution and two splice junction mutations were identified in the 17 beta HSD3 genes of five unrelated male pseudohermaphrodites. The substitution mutations severely compromised the activity of the 17 beta-HSD type 3 isozyme.

Steroid secretory characteristics of a virilizing adrenal adenoma in a woman.

A tumour of the left adrenal gland was identified in a woman who presented with virilization and secondary amenorrhea. Preoperatively, the plasma levels of dehydroepiandrosterone sulphate, dehydroepiandrosterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone and 5-androstene-3 beta,17 beta-diol were elevated two- to fourfold whereas those of urinary 17-ketosteroids were elevated more than tenfold. The production rate of dehydroepiandrosterone sulphate was more than 16 times that in normal women whereas those of dehydroepiandrosterone, testosterone and androstenedione were approximately twofold greater; plasma testosterone was derived almost entirely from the peripheral conversion of androstenedione. Blood was obtained by catheterization of the ovarian veins, left adrenal gland vein and inferior vena cava (at two different sites) and plasma steroid levels were determined: testosterone and cortisol levels were elevated in all blood samples whereas those of androstenedione, dehydroepiandrosterone sulphate and 11-desoxycortisol were approximately six- to eightfold, 1.5-fold and nine- to 22-fold higher in the effluent on the left adrenal gland/tumour compared with the levels in the other compartments. Blood was collected hourly for 24 h to determine steroid levels under basal conditions and, also, after ACTH treatment. Plasma cortisol levels increased markedly upon ACTH administration and fell to very low levels 11 h later, but those of androstenedione, testosterone, dehydroepiandrosterone, 5-androstene-3 beta,17 beta-diol and dehydroepiandrosterone sulphate were not affected by ACTH treatment. A histological diagnosis of cortical adenoma of the extirpated tumour was made. Tissue explants and adenoma cells were maintained in culture to characterize the steroid-metabolizing properties of the tumour. The secretion of dehydroepiandrosterone sulphate by tissue explants was highly initially, but declined to almost undetectable levels after 5 days in culture. In the presence of ACTH, dehydroepiandrosterone sulphate secretion remained elevated throughout the entire study up to 5 days. Basal secretion of dehydroepiandrosterone sulphate, androstenedione, 11-desoxycortisol, cortisol, testosterone and 11 beta-hydroxyandrostenedione by adenoma cells was either very low or undetectable. In the presence of ACTH, dibutyryl cyclic AMP or cholera toxin the secretion of dehydroepiandrosterone sulphate, androstenedione and 11-desoxycortisol increased markedly with time in culture up to 3 days, whereas the other steroids were undetected in the medium. A homogenate of adenoma tissue metabolized testosterone to androstenedione, but the conversion of androstenedione to testosterone was minimal. The findings of this study served to establish that virilization in this woman was due at least in part, to excess testosterone--and testosterone-derived 5 alpha-dihydrotestosterone--produced at extra-adrenal tissue sites almost exclusively through metabolism of tumour-secreted androstenedione.(ABSTRACT TRUNCATED AT 400 WORDS)

An evaluation of the effect of gonadotropin-releasing hormone analogs and medroxyprogesterone acetate on uterine leiomyomata volume by magnetic resonance imaging: a prospective, randomized, double blind, placebo-controlled, crossover trial.

The purpose of this study was to prospectively compare the effectiveness of administering medroxyprogesterone acetate (MPA; 20 mg/day) in either the first (protocol A) or last (protocol B) 12-week period along with a 6-month course of the GnRH analog (GnRH-a; leuprolide acetate; 1 mg/day, sc) on uterine and leiomyomata volumes and hormone (estradiol, LH, and FSH) and serum lipid (total cholesterol, triglycerides, and high and low density lipoprotein) levels. Sixteen women were randomized into protocol A or B, received either MPA or placebo along with GnRH-a, respectively, and were then crossed over at 12 weeks to placebo or MPA, respectively, for the final 12-week interval of GnRH-a therapy. Total, myoma, and nonmyoma uterine volumes were determined by magnetic resonance imaging, and serum studies were performed at the beginning of the study and at 12 and 24 weeks. In both protocols, LH and estradiol levels declined by 80-90% (P < 0.03) and 55-72% (P < 0.02) of the baseline, respectively, at 12 weeks and remained at this level at 24 weeks. There were no significant changes in the other laboratory tests between protocols or longitudinally over time. Total uterine volume decreased to 73% of the baseline at 12 weeks in protocol B (P < 0.04), but did not change in protocol A. After crossover at 12 weeks, the total uterine volume of women in protocol A decreased to 74% of the baseline (P < 0.02) at 24 weeks. Between-protocol comparisons demonstrated a greater decline in total uterine volume in protocol B than A at 12 weeks, but after cross-over, MPA addition was associated with a significant increase in total uterine volume (protocol B) compared to a decrease in protocol A at 24 weeks (P < 0.005). In contrast, although myoma volume declined in both protocols, no significant changes in myoma volume were detected within or between groups over the treatment period. Nonmyoma volume changes in protocols A and B roughly paralleled total uterine volume changes, with MPA coadministration showing a correlation with a reversal in the GnRH-a-associated decrease in nonmyomatous tissue volume.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of bicarbonate and HEPES-buffered media on pregnancy rates after intrauterine insemination with cryopreserved donor sperm.

OBJECTIVE: We compared the pregnancy rates (PRs) after intrauterine insemination (IUI) with frozen donor sperm prepared in Ham's F-10 medium (Irvine Scientific, Santa Ana, CA) with bicarbonate buffer and synthetic human tubal fluid with HEPES buffer (Irvine Scientific). DESIGN: Women (n = 101) were randomized upon entry into the program, receiving sperm prepared in either Ham's F-10 or human tubal fluid medium their first treatment cycle. If pregnancy did not occur, the alternate medium was used to prepared sperm for the following cycle. SETTING: All patients were treated in our private care center. PATIENTS: Patients entering this study were normally ovulating women undergoing IUI with frozen donor sperm. MAIN OUTCOME MEASURE: Pregnancy was used as our main outcome measure of success. RESULTS: After 324 cycles of treatment, the PR per cycle of IUI was 17.5% with sperm prepared in human tubal fluid which was significantly different (P = 0.05) from the PR (9.8%) after insemination with sperm prepared in Ham's F-10. There was no statistical difference in the number of motile cells inseminated in each of these groups. CONCLUSIONS: Transitory exposure of the sperm in Ham's F-10 medium to the environment during preparation for insemination may result in an alkalinization of the medium that has a lasting influence on sperm fertility.

Cumulative pregnancy rates for donor insemination according to ovulatory function and tubal status.

From our study of 234 cases of AID with fresh semen, we conclude the following: (1) women who do not have other infertility problems, such as ovulatory dysfunction or evidence of tubal disease, have approximately a 90% chance of pregnancy if they stay in the program for up to 12 cycles; (2) with even greater persistence (i.e., greater than 12 cycles), it is predicted that virtually 100% of these women would conceive, but this conclusion is based on extrapolated data and therefore must be interpreted with caution; (3) women with ovulatory dysfunction who are treated with CC during their AID cycles ultimately achieve the same likelihood of pregnancy as women with normal ovulatory function, but at a slower rate; and (4) women with one patent tube (possibly a marker for generalized tubal damage) have a poorer outcome from AID than those with bilaterally patent tubes, from the standpoint of both the ultimate likelihood of pregnancy and the pregnancy rate per cycle.

Characterization of complementary deoxyribonucleic acid for human adrenocortical 17 alpha-hydroxylase: a probe for analysis of 17 alpha-hydroxylase deficiency.

To provide a basis for investigation of the molecular mechanisms underlying the hormonal regulation of steroid 17 alpha-hydroxylase (P-450 17 alpha) activity in adrenal, ovary, and testis as well as human 17 alpha-hydroxylase deficiency, we have isolated from a human fetal adrenal cDNA library a cDNA sequence complementary to the mRNA that encodes the human P-450 17 alpha enzyme. Of 75,000 colonies from the library that were screened by use of a nick-translated 5'-specific bovine P-450 17 alpha cDNA probe, 10 positive colonies were isolated and the clone with the longest insert (pcD-17 alpha H) was selected for further characterization. pcD-17 alpha H encodes the complete human P-450 17 alpha protein having approximately 78% homology at the nucleotide level and 71% homology at the amino acid level when the sequence of pcD-17 alpha H is compared to the bovine P-450 17 alpha cDNA sequence. By transient expression of the human P-450 17 alpha cDNA clone in COS 1 cells, we have demonstrated that the 17 alpha-hydroxylase and 17,20 lyase activities reside within the same human P-450 17 alpha polypeptide chain. The insert was also used as a probe to investigate, by means of Southern blot analysis, possible alterations in the P-450 17 alpha gene sequence in DNA isolated from skin fibroblasts from three patients with clinically characterized 17 alpha-hydroxylase deficiencies. No changes were detected in the DNA of any of the patients by this analysis.

Ovarian and tubal inguinal hernia.

An inguinal hernia containing an ovary and fallopian tube is an extremely rare occurrence in a woman of reproductive age. When ovarian and fallopian tube inguinal hernias are found, they are commonly associated with defects in genital tract development. In this report a woman with primary amenorrhea, 46XX karyotype, mullerian agenesis, and an inguinal hernia consisting of an ovary and a fallopian tube is presented. The defect in embryologic development that leads to this disorder and a review of previous reports of ovarian and tubal inguinal hernias are discussed.

Placental sulfatase deficiency: maternal and fetal expression of steroid sulfatase deficiency and X-linked ichthyosis.

PSD-X-linked ichthyosis are manifestations of a similar disorder of an inborn error of metabolism characterized by a deficiency of steroid sulfatase. The decreased enzyme activity is due to the absence of the expression of enzyme (steroid sulfatase) protein. Affected individuals with this disorder are males (X-linked inheritance) with a frequency of 1/2000 to 1/6000 births. Homozygous females from cosanguineous marriages have been reported with this disorder. The diagnosis is suspected and confirmed by: Low estriol excretion; Negative DHEAS loading test Increased DHEAS in amnionic fluid; Normal DHEAS in cord plasma; Possible delayed or abnormal labor patterns; Decreased sulfatase activity in the placenta, fibroblast, erythrocytes, lymphocytes or leukocytes of affected individuals; Development of ichthyosis in male infants at 2 to 3 months of age.

Endocrine studies in a pregnancy complicated by ovarian theca lutein cysts and hyperreactio luteinalis.

Severe virilization developed in a pregnant woman in association with the occurrence of theca lutein cysts and hyperreactio luteinalis of the ovaries. At term, maternal serum levels of androstenedione (58 ng/mL) and testosterone (20 ng/mL) were elevated massively; estrone (24 ng/mL) and estradiol-17 beta (23 ng/mL) levels were increased moderately. Maternal serum levels of human chorionic gonadotropin (hCG) just before delivery, 22,276 mlU/mL, though twice the mean for normal women at term, were within the normal range. The levels of androstenedione (1.06 ng/mL) and testosterone (0.26 ng/mL) in umbilical cord serum of her normal newborn female infant were normal. The levels of androstenedione and testosterone in serum of this woman declined slowly, but progressively, during the first two months after delivery; the serum levels of androstenedione and testosterone increased substantially, however, after she was treated with hCG eight weeks postpartum. These results are suggestive that, for reasons unknown, markedly increased androgen production with theca lutein cysts and hyperreactio luteinalis in some pregnant women results ultimately because of increased ovarian sensitivity to hCG.