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Biomedical subjects

B R Carr

Publications and source records attributed to B R Carr.

At least 37 records · Page 2Linked to original sources
PubMed1997

Re-evaluation of oral contraceptive classifications.

Classification of combination oral contraceptives (OCs) by "generation"--typically based on the time of introduction of new compounds--is problematic. The estrogen and progestin components may be present in differing doses, and their interaction may therefore vary from one formulation to another. In addition, assigning the progestin component itself to a particular generation does not account for the unique characteristics of individual progestins within that group. These issues can be clarified by understanding the evolution of combination OCs in relation to dosage changes and by differentiating the pharmacologic profiles of individual progestins, particularly norgestimate, desogestrel, and gestodene. Although all sex steroids have the same basic structure, relatively minor structural modifications can cause dramatic alterations in biochemical activity. Progestational activity is the desired pharmacologic effect of progestins used in OCs, whereas androgenic activity, which increases the potential for adverse metabolic and physical side effects, is undesired. In vitro assays of the ability of various OC progestins to bind progestin and androgen receptors suggest that the androgen/progestin (A/P) binding ratio--a measure of progestin selectivity--is more favorable for norgestimate than for levonorgestrel, gestodene, or desogestrel. In vivo measurements of interactions between various progestins and human sex hormone binding globulin (SHBG) support the concept that generational classification of OC progestins is misleading. These compounds also differ clinically, as exemplified by differential effects on lipoprotein metabolism. In summary, progestins exhibit individually unique biochemical and clinical properties.

Animals↗
PubMed1996

HRT management: the American experience.

OBJECTIVES: To review the history, current clinical practice, choice of methods and number of prescriptions and sales of hormone replacement therapy (HRT) in the US. METHODS: Literature review, survey data collection, sales and prescription data. RESULTS: The number of women currently utilizing HRT is greater in women aged 40-60 (35%) but falls with advancing age greater than 65 (15%) and declines further in women greater than 80 (7%). News media and physicians represent the largest source of information used by US women for information regarding HRT. Obstetricians and gynecologists currently are the predominant physicians prescribing HRT, but in the future, family practitioners and paramedical workers will prescribe HRT. Women who spontaneously develop menopause early and younger women undergoing castration are more likely to take transdermal estrogen. However, the majority of prescriptions in the US are oral estrogens (86% of the market). The market leader of oral estrogens in the US are conjugated equine estrogens (70%). Fifty percent of prescriptions in women with a uterus consist of combined continuous estrogen and progestogen whereas as 42% consist of cyclic estrogen and progestogen. CONCLUSIONS: It appears that although there is an increase in HRT use by postmenopausal women in the US, the actual percentage of current users remains lower than anticipated. This occurred in spite of widespread media and educational efforts of benefits of HRT. Many women still fear the risk of breast and uterine cancer as well as the side effects of estrogen (primarily bleeding) which reduces the number of women currently taking estrogen. A number of surveys suggested that most women receive their information from the media and an equal amount from their physicians. With respect to estrogen use alone the majority of prescriptions are written for women without a uterus. Transdermal estrogens are used more commonly in women in the early postmenopausal period. In women with a uterus, most US physicians prescribe a combination of estrogen plus a progestogen, but when they do they utilize oral estrogen rather than transdermal estrogen.

Adult↗
PubMed1996

The effect of transforming growth factor-beta on steroidogenesis and expression of key steroidogenic enzymes with a human ovarian thecal-like tumor cell model.

OBJECTIVE: Our purpose was to determine the effects of transforming growth factor-beta on steroidogenesis and regulation of steroidogenic enzyme expression by use of a human ovarian thecal-like tumor cell culture system. STUDY DESIGN: Human ovarian thecal-like tumor cells were treated in serum-free medium in the presence or absence of forskolin and transforming growth factor-beta 1. The accumulation of progesterone and androstenedione in the culture medium was evaluated by radioimmunoassay. The effects of forskolin with or without transforming growth factor-beta 1 on the enzymatic activity of P450c17 and 3 beta HSD, the expression of immunodetectable P450c17 protein, and the expression of messenger ribonucleic acid for P450scc, P450c17, and 3 beta HSD were determined. RESULTS: Basal steroid secretion, steroidogenic enzyme activity, enzyme protein, and messenger ribonucleic acid expression were not affected by transforming growth factor-beta 1 alone. Forskolin treatment significantly stimulated steroid production and the enzymatic activity of P450c17 and 3 beta HSD up to 10-fold above basal levels. However, transforming growth factor-beta 1 inhibited forskolin-stimulated androstenedione production to near basal levels and increased progesterone 1.4- to 2-fold while suppressing P450c17 enzyme activity to near basal levels, but it did not affect 3 beta HSD activity. Forskolin-stimulated immunodetectable P450c17 alpha protein was markedly inhibited by transforming growth factor-beta 1. In addition, transforming growth factor-beta 1 markedly inhibited the forskolin-stimulation of P450c17 messenger ribonucleic acid, while not significantly altering P450scc or 3 beta HSD messenger ribonucleic acid expression. CONCLUSION: Forskolin stimulated human ovarian thecal-like tumor cell steroidogenesis, P450c17 and 3 beta HSD activity, immunodetectable P450c17, and messenger ribonucleic acid content for P450scc, P450c17, and 3 beta HSD. Transforming growth factor-beta 1 inhibited forskolin stimulation of androstenedione production through the inhibition of P450c17 expression.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

The effect of insulin and insulin-like growth factors on the expression of steroidogenic enzymes in a human ovarian thecal-like tumor cell model.

OBJECTIVE: To determine the effects of insulin and insulin-like growth factors (IGF-I and IGF-II) on steroidogenesis and steroidogenic enzyme expression in a human ovarian thecal-like tumor cell culture model system. DESIGN: Human ovarian thecal-like tumor cells treated with forskolin and insulin IGF-I or IGF-II were evaluated for media accumulation of P and androstenedione (A) as well as 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) and cytochrome P450 17 alpha-hydroxylase (P450c17) enzyme activity. Northern analysis of cytochrome P450 side chain cleavage (P450scc), P450c17, and 3 beta HSD messenger RNA (mRNA) also was performed. RESULTS: Basal hormone secretion, enzyme activity, and mRNA levels were not affected by treatment with insulin or the IGFs. Forskolin treatment stimulated steroid production, enzyme activity, and mRNA content. Forskolin-stimulated P secretion was augmented 30% by treatment with insulin and IGFs, whereas 3 beta HSD activity was augmented twofold to threefold. Forskolin stimulated A and P450c17 activity were enhanced by treatment with insulin and the IGFs. In forskolin-treated cells. P450c17 and P450scc mRNA levels were not affected by insulin (100 nM) or IGF (10 nM) treatment; however, 3 beta HSD mRNA levels were augmented by treatment with insulin and IGFs. CONCLUSIONS: We observed that forskolin-stimulated human ovarian thecal-like tumor cell steroidogenesis, P450c17, and 3 beta HSD activity, as well as mRNA content for P450scc, 3 beta HSD, and P450c17. Insulin and the IGFs augmented forskolin-stimulated production of P and the expression of 3 beta HSD, with little effect on A production, P450scc, or P450c17 expression.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Adrenarche is associated with decreased 3 beta-hydroxysteroid dehydrogenase expression in the adrenal reticularis.

The increased production of adrenal dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) which occurs during the prepubertal period is known as adrenarche. One hypothesis for adrenarche is that alterations in intra-adrenal expression of steroidogenic enzymes within the inner reticularis zone leads to the increased production of 19-carbon steroids. We tested the hypothesis that at the time of adrenarche there is decreased expression of 3 beta HSD in the reticularis. Immunohistochemical localization of 3 beta HSD was performed and staining intensities compared between adrenal glands from children ages 4 months to 7 years (N = 11) and ages 8 to 11 years (N = 6). No difference was observed between the levels of staining in the glomerulosa and fasciculata from either age group. However, the reticularis from the older children exhibited diminished 3 beta HSD immunoreactivity. These findings suggest that as children mature there is a decreased level of 3 beta HSD in the adrenal reticularis which may contribute to the increased production of DHEA and DHEAS seen during adrenarche.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Cervical mucus anti-sperm antibodies: treatment with intrauterine insemination.

PROBLEM: To determine (1) the incidence of cervical mucus anti-sperm antibodies in infertile women, and (2) the results of treatment by intrauterine insemination. METHOD: Cervical mucus was collected the morning after urinary LH surge occurred from 153 consecutive women being treated for unexplained infertility with intrauterine insemination. Immunobead testing for IgG, IgA, IgA1, and IgA2 was performed with only actively motile sperm being counted. RESULTS: Overall, 23/153 (15.0%) of cervical mucus samples were positive for anti-sperm antibodies: 9/23 (39.1%) were only IgA-positive (62% IgA1-positive, 38% IgA2-positive), 11/23 (47.8%) were only IgG-positive, and 3/23 (13.0%) were positive for both IgA and IgG. Insemination resulted in a pregnancy in 6/23 (26.1%) of women with cervical mucus anti-sperm antibodies after 1-3 cycles. CONCLUSIONS: Testing for cervical mucus anti-sperm antibodies should be performed in cases of "unexplained" infertility, and intrauterine insemination may be an effective treatment, resulting in pregnancies in over one-fourth of couples.

Cervix Mucus↗
PubMed1996

Human ovarian tumor cells: a potential model for thecal cell steroidogenesis.

Ovarian thecal cell production of C19 steroids (i.e. dehydroepiandrosterone, androstenedione, and testosterone) is necessary to provide substrate for granulosa cell biosynthesis of estrogen; however, excessive production of C19 steroids can lead to disorders associated with androgen excess. Because of difficulties in obtaining adequate numbers of thecal cells, the biomolecular regulation of C19 steroid production and expression of steroidogenic enzymes is not well defined. We have overcome this obstacle by developing a highly dependable and unique human ovarian thecal-like tumor (HOTT) cell culture model system from an ovarian tumor found to produce excessive amounts of C19 steroids. Aliquots of freshly dispersed tumor cells were frozen for future use. Once placed in monolayer culture, HOTT cells proliferated and could be maintained for extended periods. Acutely, cultured HOTT cells increased progesterone and cAMP production in response to 2 h of forskolin treatment. These cells were, however, unresponsive to treatment with LH. Steroid hormone production continued in cells that were maintained in culture for up to 2 months. Analysis of the steroids produced by HOTT cells was accomplished using RIA and high performance liquid chromatography. Under basal conditions, HOTT cells produced mainly 17 alpha-hydroxyprogesterone and progesterone. Treatment with forskolin or dibutyryl cAMP (dbcAMP) increased the production of progesterone and 17 alpha-hydroxyprogesterone as well as C19 steroids. Treatment of monolayer cultures of HOTT cells with forskolin (0.01 to 20 mumol/L) or dbcAMP (0.01 to 1 mmol/L) for 48 h increased the production of androstenedione (8- to 15-fold) and progesterone (2- to 5-fold). In HOTT cells chronically treated with forskolin or dbcAMP (up to 72 h), progesterone production was observed to plateau, although the amount of androstenedione continued to increase. The enzymatic activities of both 3 beta-hydroxysteroid dehydrogenase (6-fold), and 17 alpha-hydroxylase P450 (P450c17; 9-fold) were also increased by activation of the protein kinase A messenger pathway. Treatment of HOTT cells with forskolin caused a time-dependent induction of the messenger RNAs for cholesterol side-chain cleavage P450, 3 beta-hydroxysteroid dehydrogenase, and P450c17. No changes in steroidogenic enzyme expression were observed following treatment with LH. In conclusion, these data demonstrate that certain ovarian tumor cells may serve well as appropriate models to study the molecular mechanisms regulating human ovarian thecal cell C19 steroidogenesis and the expression of steroid-metabolizing enzymes.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Human ovarian expression of 17 beta-hydroxysteroid dehydrogenase types 1, 2, and 3.

Three isozymes of 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) have been cloned and characterized as distinct gene products (17 beta HSD1, 17 beta HSD2, and 17 beta HSD3). The presence and location of these isozymes in the human ovary have not been defined. In this study, we utilized Northern analysis and RT-PCR to examine transcripts for the three isozymes of 17 beta HSD. RNA was isolated from ovarian cortex, stroma (pre- and postmenopausal), hilum, follicles, and corpora lutea obtained from adult women, as well as whole fetal ovaries. By Northern analysis, high levels of 17 beta HSD1 messenger RNA were found in follicles, corpora lutea, and cortex, whereas low levels were detected in the postmenopausal stroma and in fetal ovaries by RT-PCR. 17 beta HSD1 messenger RNA was not detected in hilar tissue by either Northern analysis or RT-PCR. Utilizing RT-PCR, transcripts for 17 beta HSD2 were not detectable in cortex, stroma, (pre-or postmenopausal), hilum, or follicles, but were present in RNA derived from the corpora lutea and fetal ovary. The androgenic isozyme 17 beta HSD3 was not detectable in any of the ovarian compartments examined by either Northern analysis or RT-PCR. These data provide additional insight into the mechanism of testosterone and estradiol synthesis within the ovary. Specifically, the high level of 17 beta HSD1 is clearly localized to follicles and corpora lutea indicating involvement in the synthesis of estradiol. Secondly, androgenic 17 beta HSD3 is not expressed in the human ovary. Thus testosterone production within the human ovary, occurring under physiological conditions, arises from either the 17 beta HSD1 or an uncharacterized isozyme.

17-Hydroxysteroid Dehydrogenases↗
PubMed1996

A role for epidermal growth factor in the morphological and functional maturation of the adrenal gland in the fetal rhesus monkey in vivo.

We determined the effects of epidermal growth factor (EGF) and beta-methasone on the growth and development of the adrenal gland of the fetal rhesus monkey in vivo between 121-128 days of gestation. The adrenal to body weight ratio was significantly greater (P < 0.05) in EGF-treated fetuses (0.988 +/- 0.046 x 10(-3) g/g) and significantly reduced (P < 0.05) in beta-methasone-treated fetuses (0.401 +/- 0.056 x 10(-3) g/g) compared with that in control fetuses (0.689 +/- 0.050 x 10(-3) g/g). The increase in adrenal weight with EGF administration was due to hypertrophy of definitive zone cells of the adrenal cortex, whereas the reduction in adrenal weight after beta-methasone treatment was due to a decrease in the size of definitive and fetal zone cells of the adrenal cortex. By Western analysis, EGF treatment induced a significant (P < 0.05) 2.8-fold increase in the amount of protein for 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta HSD) in the fetal adrenal. EGF also stimulated the induction of immunocytochemical staining for 3 beta HSD in transitional zone cells of the adrenal cortex. In contrast, beta-methasone resulted in 2.6-, 4.5-, and 6.6-fold significant decreases (P < 0.05) in the amount of protein for cytochrome P450 cholesterol side-chain cleavage, cytochrome P450 17 alpha-hydroxylase/17,20-lyase, and 3 beta HSD in the fetal adrenal. After beta-methasone treatment. 3 beta HSD staining was detected in some of the definitive zone cells, with no 3 beta HSD staining in the transitional zone. In conclusion, growth and functional differentiation of fetal primate adrenal gland can be accelerated prematurely by EGF and inhibited by glucocorticoid negative feedback.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Inhibin and activin differentially regulate androgen production and 17 alpha-hydroxylase expression in human ovarian thecal-like tumor cells.

Activin and inhibin are structurally related dimeric glycoproteins belonging to the transforming growth factor-beta superfamily of proteins which are synthesized and secreted by the granulosa cells of the ovary. Although initially characterized by their ability to influence FSH secretion from pituitary cells, paracrine regulatory roles of these factors on neighboring ovarian theca interna have been suggested. While inhibin has been shown to increase and activin to decrease the production of androgens, the mechanisms of action are not well defined, partly due to difficulties in obtaining adequate numbers of thecal cells from individual patients or animal models. Using a unique human ovarian thecal-like tumor (HOTT) cell culture model system we investigated the biochemical and molecular mechanisms controlling C19 steroidogenesis and the effects of activin and inhibin on the activity and expression of key ovarian thecal steroidogenic enzymes, cholesterol side-chain cleavage cytochrome P450 (P450scc), 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) and 17 alpha-hydroxylase/17,20 lyase cytochrome P450 (P450c17). Steroid production, level of steroidogenic enzyme mRNA expression, and enzyme activity following treatment with forskolin, inhibin-A and activin-A were examined. Basal steroid production, enzyme activities, and steroidogenic enzyme mRNA levels were not markedly different following treatment with activin (25 ng/ml) or inhibin (25 ng/ml) alone. Forskolin (10 microM) markedly increased production of both androstenedione (fivefold) and progesterone (threefold) as well as the activity of 3 beta HSD (sevenfold), and P450c17 (sevenfold) over basal. Forskolin stimulated the expression of mRNA for P450scc (fourfold), 3 beta HSD (threefold), and P450c17 (eightfold) over basal. Androstenedione accumulation was decreased by 60% in the forskolin plus activin group compared with forskolin alone, while progesterone production was maintained. This was attributed to a reduction of P450c17 mRNA (45% of forskolin alone) and activity (45% of forskolin alone). In contrast, co-treatment with forskolin and inhibin increased androstenedione production by 40% while decreasing progesterone by 40% compared with forskolin alone. Concomitantly, this was associated with a higher P450c17 mRNA expression (1.5-fold) and activity (twofold) but with minimal effects on the mRNA for 3 beta HSD and P450scc. HOTT cell responses to activin (0.05-50 ng/ml) and inhibin (0.05-50 ng/ml) in the presence of forskolin demonstrated dose-dependent effects on the steroid accumulation, enzymatic activity and mRNA expression of P450c17. Additionally, the differences seen on mRNA expression of steroidogenic enzymes in response to these factors were time-dependent. In summary, forskolin stimulated C19 steroid production from HOTT cells by increasing the expression of all steroidogenic enzymes examined. Inhibin and activin exerted differential effects on the expression of these enzymes which resulted in alterations in the steroid profile toward production of C19 steroids in the case of inhibin and away from C19 steroids in the case of activin. The influence of these important intraovarian factors on the expression of P450c17, a pivotal enzyme in thecal cell production of C19 steroids, could impact greatly on the follicular milieu of a normal developing follicle as well as in pathophysiological disorders such as polycystic ovarian syndrome.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

The effect of gonadotropin-releasing hormone agonist on thyroid-stimulating hormone and prolactin secretion in adult premenopausal women.

OBJECTIVE: To investigate the effects of chronic administration of GnRH agonists (GnRH-a) on pituitary TSH and PRL secretion in adult women. DESIGN: Prospective case-controlled study. SETTING: Academic division of Reproductive Endocrinology, Department of Obstetrics and Gynecology. PATIENTS: Ten ovulatory women and 10 women treated with monthly depot injections of leuprolide acetate (3.75 mg) were studied. INTERVENTIONS: All subjects underwent pituitary stimulation with human thyrotropin-releasing hormone (TRH), 500 micrograms IV. MAIN OUTCOME MEASURES: Basal and post-TRH-stimulated serum levels of TSH and PRL at 15, 30, 45, 60, 90, 120, and 180 minutes were compared among the two groups. Also, basal of T4, triiodothyronine, and triiodothyronine resin uptake studies were obtained and compared among the GnRH-a-treated and control groups. RESULTS: No statistically significant difference between baseline or TRH-stimulated serum TSH and PRL could be detected between control and GnRH-a-treated groups of women. Furthermore, these groups were similar with respect to routine thyroid function assays. CONCLUSION: Gonadotropin-releasing hormone agonist does not significantly affect baseline or TRH-stimulated TSH and PRL levels nor basal serum T4 and triiodothyronine levels or triiodothyronine resin uptake in adult women.

Adult↗
PubMed1995

Oral contraceptive pills, gonadotropin-releasing hormone agonists, or use in combination for treatment of hirsutism: a clinical research center study.

The effectiveness of oral contraceptive pills (OCPs), GnRH agonist (GnRH-a), and a combination of OCPs and GnRH-a in the treatment of hirsute women was compared and the impact of these treatments on hormonal and Ca metabolism was investigated. Thirty-three women were prospectively enrolled and randomized into three treatment groups (11 in each group). The serum levels of LH, estradiol, testosterone, free testosterone, androstenedione, and 17-hydroxyprogesterone declined in all 3 treatment groups, whereas the inclusion of GnRH-a treatment tended to promote a more rapid decrease in these hormone levels. Total cholesterol, low density lipoprotein, and high density lipoprotein levels remained unchanged. The assessment of hirsutism by the Ferriman-Gallwey score revealed a similar 25% reduction in score by all three treatment groups by 6 months. In addition, no difference was detected between groups with respect to hair diameters and the vellus index. Clinical assessment of hirsutism at 3 months by the patients revealed that the GnRH-a and the OCPs-plus-GnRH-a groups had better responses than the group on OCPs alone, but by 6 months all three groups were similar. The symptoms of hot flashes and vaginal dryness were greatest in subjects treated with GnRH-a alone. Serum Ca, phosphorus, alkaline phosphatase, osteocalcin, and 2-h fasting and 24-h urinary Ca excretion levels all increased significantly in subjects treated with the GnRH-a alone, whereas a decrement or no changes occurred for these measurement in the other two groups. The estimated Ca balance was unchanged in the OCPs and the OCPs-plus-GnRH-a groups but declined by 90 mg/day from baseline in the GnRH-a-treated women (p < or = 0.001). Bone density significantly decreased in the lumber spine in women treated with GnRH-a alone, with a less marked decline in the femoral neck. In contrast, women receiving OCPs plus GnRH had increased bone density in the lumbar spine. It is concluded that: 1) clinical measures of hirsutism are not different after 6 months of treatment with OCPs alone, GnRH-a alone, or a combination of the two; 2) the decline in gonadotropins and steroid hormones and improvement in clinical response were more rapid and pronounced when GnRH-a treatment was added to OCP administration; and 3) the negative impact of GnRH-a alone on Ca balance and bone loss limits its usefulness as a single agent for long-term therapy of hirsutism.

Adult↗
PubMed1995

Infertile couples with a normal hysterosalpingogram. Reproductive outcome and its relationship to clinical and laparoscopic findings.

The purpose of this study was to retrospectively investigate the clinical course of infertile couples following a normal hysterosalpingogram (HSG) to determine the reproductive outcome and assess the diagnostic value of subsequent laparoscopy (LSC). The infertile couples (N = 132) were aged 29 +/- 0.5 SD years, with 3.2 +/- 0.4 years of infertility, and were followed for an average of 17 +/- 1.5 months after the HSG. Twenty-nine percent of patients became pregnant after a normal HSG performed with water-soluble contrast medium. There was a fourfold greater rate of pregnancy during the first three months after a normal HSG than during any other three-month interval up to one year. Thirty-four of the initial 132 patients required laparoscopy because of failure to conceive or suspected pelvic disease based on symptoms or the results of a pelvic examination. Among the 34 patients receiving LSC, pelvic pathology was found in 19 (56%). Corrective surgery and/or a change in therapy occurred in 60% of cases after LSC. There was an increased proportion of abnormal findings with increasing time intervals between HSG and LSC but not with increasing intervals of infertility before HSG. Abnormal uterine bleeding was predictive of abnormalities at LSC, while prior use of oral contraceptives correlated negatively with pelvic pathology. In women in infertile couples who have a normal HSG: (1) LSC should not be performed before three months after a normal HSG because of the potential therapeutic effect of HSG, (2) LSC should be performed after a normal HSG if pregnancy has not occurred by at least one year because of the high incidence of pelvic pathology, and (3) HSG using water-soluble contrast media has a therapeutic effect comparable to that described for oil-soluble contrast media.

Adult↗
PubMed1995

Hirsutism and virilization. A systematic approach to benign and potentially serious causes.

A woman with excessive body hair may visit a physician with concerns about fertility and general health as well as appearance. Fortunately, the cause is usually benign, most often polycystic ovarian syndrome. However, life-threatening causes must be quickly ruled out. Hirsutism secondary to endocrinopathies and tumors can typically be recognized by the rapid progression of hair growth; patients should be referred for prompt evaluation and treatment. Benign causes can usually be treated effectively with medical and mechanical methods.

Female↗
PubMed1994

Compartmentalization of type I 17 beta-hydroxysteroid oxidoreductase in the human ovary.

The steroid-metabolizing enzyme, type I 17 beta-hydroxysteroid oxidoreductase (17 beta-HSOR) also called 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) plays a key role in ovarian synthesis of 17 beta-estradiol. This is the only enzyme in the steroid-metabolizing pathway which has not been localized in the human ovary by immunohistochemistry. In this study, using antibody directed against human placental cytosolic 17 beta-HSOR (type I), a single protein band with a relative molecular mass of approximately 34 kDa was demonstrated by Western analysis in both human luteinized granulosa cells and placental tissue. In placental tissue, immunoreactive type I 17 beta-HSOR was demonstrated within the syncytiotrophoblast using immunohistochemistry. In human ovary, immunoreactive type I 17 beta-HSOR was localized exclusively in granulosa cells of developing follicles, ranging from primary follicles with a single layer of cuboidal-shaped granulosa cells, preantral follicles with multiple layers of granulosa cells, and large antral follicles. No immunoreactivity was detected in spindle-shaped granulosa cells of primordial follicles, theca interna, theca externa or surrounding stroma. In the corpus luteum, type I 17 beta-HSOR immunoreactivity was localized solely in granulosa-lutein cells. For comparison, immunoreactive 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) was examined in the same tissues. Both theca interna and granulosa cells of preantral and antral follicles exhibited 3 beta-HSD staining. Primary follicles did not exhibit detectable 3 beta-HSD in either granulosa or theca cells.(ABSTRACT TRUNCATED AT 250 WORDS)

17-Hydroxysteroid Dehydrogenases↗
PubMed1994

Evaluation of clomiphene citrate and human chorionic gonadotropin treatment: a prospective, randomized, crossover study during intrauterine insemination cycles.

OBJECTIVE: To test the hypothesis that in couples undergoing IUI, actively managed cycles using clomiphene citrate (CC) stimulation, ultrasound monitoring, and hCG timing will result in increased pregnancy rate (PR) per cycle compared with unstimulated urinary LH-timed cycles. PATIENTS: Fifty-six couples with unexplained infertility (n = 26) or male factor infertility (n = 30) participated in the study. SETTING: Tertiary academic medical center. DESIGN: Prospective, randomized, crossover. Couples were randomized initially to one of the two study groups (treatment A: LH-timed IUI; treatment B: CC-stimulated, hCG-timed IUI). If no pregnancy occurred, each couple alternated between the two regimens during subsequent cycles, up to a total of four cycles. RESULTS: Twenty-nine couples completed the study and the analysis of 95 cycles revealed that among the male factor infertility group, one pregnancy occurred during the 26 cycles of each treatment group (PR per cycle of 3.9% for both treatment groups). In contrast, among the unexplained infertility group, there was a marked difference in the effect of treatments. During treatment A only one pregnancy occurred in 20 cycles (PR of 5% per cycle) whereas during treatment B, six pregnancies occurred in 23 cycles (PR of 26.1% per cycle). CONCLUSIONS: If IUI is chosen as the treatment modality in unexplained infertility, the addition of active ovulation management that includes CC stimulation, ultrasound monitoring of folliculogenesis, and hCG timing of ovulation increases the PR per cycle. In couples with male infertility, PR per cycle is low and is apparently not affected by the addition of active ovulation management.

Adult↗
PubMed1994

Intrauterine insemination with frozen donor sperm: a prospective randomized trial comparing three different sperm preparation techniques.

OBJECTIVE: To compare the pregnancy rates (PRs) after intrauterine insemination (IUI) with frozen-thawed donor sperm. Sperm were isolated after thawing using three different sperm preparation techniques: simple washing, Percoll density gradient, and Sephadex columns (SpermPrep Column; Fertility Technologies, Natick, MA). DESIGN: Women (n = 98) were randomized upon entry into the program into one of three different sperm preparation methods. The same sperm preparation technique was used for the woman during subsequent cycles, if pregnancy did not occur. The study was stopped when > or = 75 treatment cycles for each group were completed for analysis of PRs per treatment cycle. SETTING: All patients were treated at our private care center at the University of Texas Southwestern Medical Center. PATIENTS: Patients entering this study were spontaneously ovulating women undergoing IUI with frozen donor sperm. MAIN OUTCOME MEASURE: Pregnancy rate per cycle of timed IUI. RESULTS: After 260 cycles of insemination, the PR per cycle was 19.1% with simple washing, 16.9% with Sephadex columns, and 11.4% with Percoll density gradient. Although these results were not statistically different, Percoll density gradient had a 40% lower PR per treatment cycle compared with simple washing. However, Percoll density gradient preparation of sperm resulted in a statistically significant increase in the motility, curvilinear velocity, straight line velocity, and the number of normal heads compared with the other two treatments. CONCLUSION: Although Percoll density gradient separation of sperm results in a population of cells that is more motile and morphologically normal, this did not result in subsequent cycle fecundity. These data suggest that the reliance on the averaged values of motility, curvilinear velocity, straight line velocity and morphology may have little predictive value of the potential fertility of frozen-thawed sperm.

Adult↗