PubMed Health⌕ Search

Biomedical subjects

K L Peh

Publications and source records attributed to K L Peh.

At least 19 recordsLinked to original sources
PubMed2002

Evidence for the biosynthesis of DHEA from cholesterol by first-trimester human placental tissue: source of androgens.

With a view to establishing whether first-trimester human placentas possess the ability to synthesize DHEA from cholesterol, homogenates of this tissue obtained from two groups of women undergoing elective termination of normally progressing pregnancy between 10 - 12 weeks gestation (n = 5, age 23 - 29 years and n = 5, age 21 - 27 years) were incubated separately with [26-(14)C]cholesterol for the generation of [14C]isocaproic acid + pregnenolone and [7n-3H]pregnenolone for the biosynthesis of [3H]DHEA. Controls consisted of homogenates heated in a boiling water bath for 10 min. Using the reverse-isotope dilution analysis, desmolase efficiency expressed as mean specific activity of [14C]isocaproic acid varied from 282 to 725 dpm/mmol, while that of 17 alpha-hydroxylase and steroid C-17,20-lyase, catalyzed conversion of [7n-3H]pregnenolone to [3H]DHEA varied from 3498 to 26 258 dpm/mmol. The corresponding efficiencies of enzymicconversion varied between 5.8 x 10( -2) and 1.5 x 10( -1) % for [14C]isocaproic acid, but between 5.5 x 10( -2) and 4.1 x 10( -1) % for [3H]DHEA. No such metabolite was evident in the controls of heat-denatured homogenates. These are the first study results to demonstrate that early placentas are capable of converting cholesterol to pregnenolone to DHEA, contrary to the widely held concept of DHEA production by fetal and maternal adrenal glands. This finding has important physiological implications and could provide a new dimension to the concept of fetoplacental steroidogenesis.

Adult↗
PubMed2001

Enhanced dehydroepiandrosterone synthesis by amnion compared to chorion: a comparative study using the reverse-isotope dilution technique.

With a view to establishing whether the term human fetal membranes possess the enzymic ability to synthesize dehydroepiandrosterone (DHEA) from pregnenolone, homogenates of amnion and chorion obtained from women (n = 5, age 27-34 years) after spontaneous labor at term (37-42 weeks gestation) from uncomplicated pregnancies were incubated with [7n-3H]pregnenolone as substrate. Reverse-isotope dilution analysis gave positive identification of [3H]DHEA acetate in all incubations of viable tissues. No such metabolite was evident in control incubations with heat-denatured tissues. Virtually radiochemically pure esters under three recrystallizations were obtained with mean concentrations of between 15787 and 30137 dpm mol(-1) for amnion which was considerably higher than that of chorionic tissues at 4316-5528 dpm mol(-1). The magnitude of elevation in DHEA production by amnion was noted to be between 3.6- and 5.5-fold higher than the corresponding chorion. This study provides evidence that the fetal membranes possess 17-alpha hydroxylase and C-17, 20 lyase activities capable of synthesis of DHEA, an important androgen necessary for aromatization to estrogens in need by the developing fetus.

Amnion↗
PubMed2000

Evidence for progesterone synthesis by human umbilical cord blood erythrocytes.

In order to determine whether human umbilical cord blood erythrocytes are capable of progesterone biosynthesis, sonicated preparations of plasma-free erythrocytes at the range of total cell numbers between 18.4 x 10(9) and 62.9 x 10(9) cells obtained from umbilical cord arterial and venous blood collected from normal pregnant women (n = 6, age 28-39 years) following spontaneous vaginal delivery were incubated with [7n-(3)H]-pregnenolone as substrate. The leucocyte content of the incubates was negligible (<0. 005%). Controls (n = 4, age 29-36 years; 27.6 x 10(9) to 42.7 x 10(9) erythrocytes) obtained from cord blood of normal pregnant women were heat-denatured preparations of cells. Using the reverse-isotope dilution technique, [(3)H]-progesterone was isolated and characterized yielding an overall enzymic conversion which ranged between 0.27 and 0.46%. The results indicate for the first time that cord blood erythrocytes possess the 3beta-hydroxysteroid dehydrogenase-5,4-en isomerase activity and are a source of progesterone in human pregnancy.

Adult↗
PubMed2000

Evidence for de novo cholesterol synthesis by term human fetal amnion and chorion: a comparative study using the reverse-isotope dilution technique.

The cholesterol biosynthetic activity was assessed using [2-(14)C]-acetate as substrate in the homogenates of amnion and chorion obtained from women (n = 6, age 26-39 years) after spontaneous labour at term (37-40 weeks of gestation) having uncomplicated pregnancies. Reverse-isotope dilution analysis gave positive identification of [(14)C]-cholesterol acetate in all incubations of viable tissues. This metabolite was not evident in heat-denatured homogenates which served as controls. The extent of enzymic conversion for amnion at 2.6 x 10(-3) to 0.19% was persistently higher than that of the chorion at 1.7 x 10(-3) to 9.0 x 10(-3)%. The results indicate that human term fetal membranes possess the full complement of enzymes to catalyze the transformation of acetate to cholesterol. This study provides evidence that fetal membranes possess the capacity for de novo cholesterol biosynthesis, the sterol being essential for steroidogenesis as well as in embryo viability during pregnancy.

Acetates↗
PubMed1999

Expression of C-20, 22 desmolase activity by the human fallopian tube in vitro: evidence for steroidogenesis.

With a view to establishing whether cells of the human Fallopian tubes possess the cholesterol side-chain cleavage activity, homogenates of the tubes, obtained from 6 women (39-45 years) following abdominal hysterectomy for benign conditions, were incubated with (7n-3H)-cholesterol as substrate. Controls (n=6, age 40-44 years) were homogenates heated in a boiling water bath for 10 min. Using the reverse-isotope dilution technique, (3H)-pregnenolone was isolated and characterized. No such metabolite was evident in control incubations of heat-denatured enzymes. The extent of enzymic conversion varied from 1.9 x 10(-3) to 1.3 x 10(-2)%. The results reveal for the first time the existence of an active cholesterol-specific C-20, 22 desmolase system in the viable tissues. It is suggested that there exists a potential for substantial pregnenolone synthesis in vivo. This rate-limiting steroid biosynthetic conversion provides a new dimension to the functional capacity of the Fallopian tubes in the synthesis of steroids, which may be necessary for modulating ciliary beat frequency and in maintenance of hormonal milieu essential for embryogenesis.

Adult↗
PubMed1998

Expression of 3beta-hydroxysteroid dehydrogenase-5,4-en isomerase activity by infiltrating ductal human breast carcinoma in vitro.

In order to determine whether human mammary tumors could contribute to progesterone synthesis from pregnenolone in breast cancer patients, homogenates of infiltrating ductal primary breast tumors at different stages of malignancy (Stages II and III) obtained from pre- and post-menopausal patients (n = 7, age 37-66 years) were incubated with [7n-3H]pregnenolone as substrate. Controls were heated homogenates instead of fresh homogenates. With the use of reverse-isotope dilution analysis, [3H]progesterone was isolated and characterized. No such metabolite was evident in the control incubations of heat-denatured enzymes. The extent of enzymic conversion varied from 0.02 to 4.0%. The results reveal that activity of 3beta-hydroxysteroid dehydrogenase-5,4-en isomerase that metabolizes pregnenolone to progesterone can be identified with the viable homogenates. It is suggested that there exists a potential for substantial progesterone synthesis in vivo. This conversion may be of considerable clinical, therapeutic, and pathophysiological significance in the patient with breast cancer. The biological impact of this conversion should be a high priority research objective.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

A comparative study of progesterone synthesis by term human fetal amnion and chorion.

Activity of 3 beta-hydroxysteroid dehydrogenase-5, 4-en isomerase was investigated with [7n-3H] pregnenolone as substrate in the homogenates of amnion and chorion collected from women (n = 6, age 20-34 years) after spontaneous labour at term (37-40 weeks gestation) from uncomplicated pregnancies. Controls were heat-denatured homogenates instead of fresh homogenates. Reverse-isotope dilution analysis gave positive identification of [3H] progesterone in all incubations of viable tissues. This metabolite was not evident in the controls. The extent of enzymic conversion of chorion, 1.4-31.1% was consistently higher than that of the amnion, 0.66-1.7%. The results show that the human fetal membranes can be a source of progesterone during pregnancy. The metabolic capability may have physiological significance in the induction and progression of labour to parturition.

Amnion↗
PubMed1994

A relationship between sperm count and intracellular progesterone, 17 alpha-hydroxyprogesterone, and cortisol concentrations in human spermatozoa.

In an attempt to determine whether human spermatozoa contain steroid hormones, in this study we have measured the immunoreactive levels of P, 17 alpha-OHP, and F in the extracts of sonicated specimens of sperms obtained as ejaculates from husbands of infertile couples. The results of this study demonstrate for the first time that human spermatozoa contain definite amounts of the measured steroids and suggests an association between steroid levels and sperm count. These steroids identified intracellularly in the haploid germ cells may play a role in the molecular events associated with fertilization.

17-alpha-Hydroxyprogesterone↗
PubMed1993

Response of ovary in young women experiencing laparoscopy under general anaesthesia.

This study investigated whether changes in circulating levels of immunoreactive oestradiol-17 beta (E2), progesterone (P) and testosterone (T) occur in women at follicular (n = 18, age 25 to 39 years) and luteal (n = 17, 25 to 39 years) phases of the normal menstrual cycles, experiencing laparoscopy after intravenous sedation with general anaesthesia. The pre- and intra-operative follicular phase plasma steroid hormone concentrations were 153.5 +/- 84.3 vs 297.4 +/- 220.8 pg/ml for E2, 2.0 +/- 3.2 vs 3.3 +/- 3.8 ng/ml for P and 746.6 +/- 415.9 vs 1325.8 +/- 535.1 pg/ml for T, respectively. The corresponding luteal phase steroid levels were 259.7 +/- 120.2 vs 382.7 +/- 188.7 pg/ml, 7.0 +/- 4.8 vs 9.9 +/- 6.1 ng/ml and 819.4 +/- 355.7 vs 1703.5 +/- 1058.1 pg/ml. Using the Wilcoxon rank sum test, intra-operative hormone levels with the exception of P in the luteal phase were found to be significantly elevated (p < 0.05). The results suggest that laparoscopy under general anaesthesia evokes increased secretion of ovarian hormones, possibly via the activation of hypothalamo-pituitary-ovarian axis.

Adult↗
PubMed1992

In vitro formation of testosterone via the delta 5-pathway in the human umbilical cord.

Homogenates of two groups of term umbilical cord (n = 6, 37-40 weeks; n = 6, 38-40 weeks) were separately incubated with [7n-3H]pregnenolone and [1,2,6,7-3H]dehydroepiandrosterone. Using the reverse-isotope dilution technique, [3H]dehydroepiandrosterone and [3H]testosterone formed from the respective substrates were isolated and characterized. The extent of enzymic conversions were 0.015-0.28% and 0.044-2.2%. These results provide evidence for the metabolic transformation of pregnenolone to testosterone via the delta 5-3 beta-hydroxy route.

Chromatography↗
PubMed1991

Human umbilical cord as a possible source of progesterone.

Homogenates of human term umbilical cord were incubated with 7n-3H-pregnenolone. Using a reverse-isotope dilution technique, 3H-progesterone was isolated and characterized. The extent of enzymic conversion ranged from 2.5 to 55.4%. The results indicate that the cord can be a source of progesterone during human pregnancy.

Adult↗
PubMed1990

Elevated peritoneal fluid luteinizing hormone and prolactin concentrations in infertile women with endometriosis.

In this study, we compared (Mann-Whitney U-test) the peritoneal fluid FSH, LH and PRL levels, measured by RIA, at the follicular and luteal phases of the menstrual cycle in women with (n = 43; age 25-44 years) and with no evidence of endometriosis (n = 35; age 25-39 years) who were considered as controls. Both follicular and luteal phase FSH concentrations of women with endometriosis were not statistically different (n = 22 vs 18; 0.32-5.8 vs 0.50-8.2 IU/l, P = 0.247; n = 13 vs 14; 0.6-6.5 vs 0.66-6.7 IU/l, P = 0.604) compared to their respective controls. In contrast to FSH, the concentrations of LH at follicular (n = 19 vs 17; 3.1-34.2 vs 2.3-12.2 IU/l, P = 0.01) and luteal (n = 17 vs 15; 2.1-95.4 vs 1.3-17.9 IU/l, P = 0.02) phases of the test group was significantly elevated at both phases of the cycle. With respect to differences in PRL concentrations at follicular phase no significant change (n = 21 vs 16; 1030-5800 vs 1305-4650 mIU/l; P = 0.255) was observed. The greatest difference in luteal PRL concentrations (P = 0.007) was obtained between the women with endometriosis and controls (n = 17 vs 17; 1895-8600 vs 1041-5000 mIU/l). The results suggest that disordered synchronization of neuroendocrine mechanisms controlling LH and PRL may be the underlying abnormality causing infertility in our group of patients with endometriosis.

Adult↗
PubMed1990

Cholesterol side-chain cleavage activity in the human umbilical cord in vitro.

With a view to establish whether cells of the human umbilical cord possess cholesterol side-chain cleavage activity, homogenates of term umbilical cord obtained following spontaneous vaginal delivery from uncomplicated pregnancies (n = 6; 38-40 weeks gestation) were incubated with 26-14C cholesterol. Controls were homogenates heating in a boiling water bath for 10 min. Proof of the existence of cholesterol C-20, 22-desmolase activity in the viable tissue was established by associating radioactivity due to the labelled carbon 26 of 26-14C cholesterol with the p-bromophenacyl ester of isocaproic acid by reverse-isotope dilution analysis. The desmolase efficiency expressed as specific activity of 14C isocaproic acid, dpm g-1 tissue varied from 110 to 351 with a mean of 202. The small but definite conversion indicates that the cholesterol side-chain cleavage reaction previously believed to be exclusive to the steroidogenic pathway operating in the adrenal, gonads and placenta does exist in the human term umbilical cord in vitro.

Adult↗
PubMed1989

Upper genital tract fluid oestradiol-17 beta, progesterone and testosterone concentrations during the menstrual cycle.

This study was to obtain evidence whether a cyclical pattern in the concentrations of oestradiol-17 beta, progesterone and testosterone exists in the upper genital tract fluid of women with normal menstrual cycles. The steroid concentrations at proliferative and luteal phases were n = 20 vs 17, 54.5-190.0 vs 44.2-827.1 pg/ml; 0.27-3.3 vs 3.4-46.5 ng/ml and 41.9-734.8 vs 85.7-991.2 pg/ml, respectively. The results were analysed according to Mann-Whitney U test. Significantly higher concentrations of oestradiol-17 beta (p = 0.0036) and progesterone (p = 0.0001) were found. The results suggest the existence of a cyclical variation and point to the ovary as the main source of output of the steroids.

Adult↗
PubMed1988

Comparison of AFP and beta-hCG levels in infiltrating duct mammary carcinoma at different stages of malignancy.

In order to assess the likely clinical value of AFP and beta-hCG levels as markers of the extent of spread of infiltrating duct mammary carcinoma, we compared (Mann-Whitney U test) the immunoreactive tumour tissue concentrations of the respective antigens, measured by specific RIA, after mastectomy in Chinese women at stages I (n = 9), II (n = 13) and III (n = 7) with that of normal breast tissue (n = 11). Elevated concentrations of the oncofetal antigens were found at all stages of malignancy. The discovery of an hCG-like material in the extract of normal breast tissues indicates limited value of beta-hCG assay in mammary tumours. However, our findings generally suggest that measurement of the tumour tissue AFP levels warrant consideration as a useful biochemical marker for in-vitro evaluation of tumour spread at all stages of malignancy.

Adult↗