Biomedical subjects

S Belisle

Publications and source records attributed to S Belisle.

At least 37 records · Page 2Linked to original sources

PubMed1986

The relation of endometriosis to menstrual characteristics, smoking, and exercise.

We compared menstrual characteristics and constitutional factors in 268 white women with primary infertility due to endometriosis and in 3,794 white women admitted for delivery at seven collaborating hospitals from 1981 to 1983. Adjusting for confounding factors, including location, age, religion, and education, women with short-cycle lengths (less than or equal to 27 days) and longer flow (greater than or equal to one week) had more than double the risk for endometriosis compared with women with longer cycle lengths and shorter duration of flow. There was a trend for increasing risk for endometriosis to be associated with increasing menstrual pain. Adjusting for these menstrual characteristics, we found decreased risk for endometriosis associated with smoking or exercise that was largely confined to women who began either habit at an early age and were heavier smokers or more strenuous exercisers. We conclude that risk for endometriosis may relate to menstrual factors that predispose to greater pelvic contamination with menstrual products and to constitutional factors that influence endogenous hormonal levels.

Adolescent↗

PubMed1986

Decreased nuclear binding of estrogen receptors in the pituitary of mice: correlation with biological effects throughout aging.

We have determined the biological impact of our previously reported decreased activation of pituitary E2 receptors (PER) in mice. Young (4-8 months), middle-aged (10-14 months) and aged (15-18 months) female mice were studied either intact (metestrous) or gonadectomized (ovx) for 2 weeks prior to decapitation. Recombination studies using heat-treated cytosolic PER and enriched nuclear fractions of various age groups showed a markedly reduced ability for nuclear binding with advancing age, despite unchanged affinity of activated PER for nuclear acceptor sites. Cross incubation studies of heat-activated cytosolic PER with nuclei from mice of various age groups suggested that the activation defect followed the onset of anestrous whereas a reduced nuclear ability to support receptor binding preceded this manifestation. In parallel with these endocrine changes we observed a decrease in baseline cytosolic progesterone receptor (RcP) concentration and in the activity of the enzyme G6PDH in intact aging mice. Ovx induced a further decrease of both markers in young and middle-aged, but not in old mice, while E2 administration induced a decreased pituitary response in RcP but not in G6PDH in aged mice. Our results suggest functional changes in cytosolic nuclear interactions in the pituitary of aging female mice.

Aging↗

PubMed1986

On the role of luteinizing hormone-releasing hormone in the in vitro synthesis of bioactive human chorionic gonadotropin in human pregnancies.

The dynamics of luteinizing hormone-releasing hormone (LHRH) induced human chorionic gonadotropin (hCG) production were studied in isolated placental cells from normal and anencephalic midterm and term gestations. A spontaneous release of immunoreactive hCG was first detected after 24-36 h of preparation in term control cells. The addition of LHRH at a concentration ranging from 10(-9) to 10(-6) M induced a threefold increase in this output of hCG. Placental cell responsiveness to LHRH varied according to the number of days of cell cultures, with maximal response on days 1 and 6. Placental cells from normal pregnancies incubated with 1 X 10(-6) M LHRH showed a release of both immuno- and bio-assayable hCG, which was four- to six-fold higher at midgestation than at term (p less than 0.001). In contrast, placental cells from pregnancies with anencephalic fetuses showed, at both stages of gestation, an hCG production that was comparable to that observed with normal term placental cells. We conclude that LHRH at a concentration appropriate for its placental receptor binding affinity induces a production of bioactive hCG in humans. Furthermore, our data suggest that anencephaly changes the placental response of hCG to LHRH stimulation.

Anencephaly↗

PubMed1986

Effect of aging on the dissociation kinetics and estradiol receptor nuclear interactions in mouse uteri: correlation with biological effects.

The dissociation kinetics of uterine estradiol receptor (UER) from young, middle-aged, and old mice have been studied in vitro and correlated with interactions of the steroid receptor with nuclear suspensions in a cell-free system. Furthermore, we have determined in these various age groups of mice the concentration of uterine cytosolic progesterone receptors and the activity of glucose-6-phosphate dehydrogenase. Compared to UER from young mice, the receptor from middle-age and old mice displayed similar first order dissociation kinetics, but a significantly reduced fraction of the slow component resulting from transformation of the receptor into a state of higher affinity for estradiol. In all age groups, sodium molybdate markedly inhibited this heat activation of UER. Recombination studies using heat-treated cytosolic UER and enriched nuclear fractions of various age groups suggested a markedly reduced ability for nuclear binding with advancing age, despite unchanged affinity of activated UER for nuclear acceptor sites that ranged from 3-5 X 10(9) M-1. Cross-incubation studies of heat-activated cytosolic UER with nuclei from young, middle-aged, and old mice suggested that the activation defect of cytosolic UER was already present at middle age and that a reduced nuclear ability to support receptor binding followed the onset of reproductive acyclicity. In parallel with these endocrine defects, we observed, with aging, decreases in mean baseline progesterone receptor concentrations and glucose-6-phosphate activity in uteri of both intact and castrated mice. The diminution of these two parameters was present at middle age, further increased at old age, and persisted after administration of low (0.2 mg) or high (2.0 mg) doses of estradiol for 3 days before study. Our observations suggest that decreased receptor activation is primarily responsible for the decreased effects of estrogen in aging mice.

Aging↗

PubMed1986

Clinical efficacy and safety of cyproterone acetate in severe hirsutism: results of a multicentered Canadian study.

We compared the efficacy and safety of cyproterone acetate (Shering AC, Berlin, FRG) at a low (Diane, 2 mg) or a high dose (Androcur, 100 mg) in the treatment of 158 patients with severe hirsutism. At baseline, no difference was observed in mean hirsutism total index (19.5 Diane versus 20.1 Androcur) or distribution (facial, bust, or abdomen). By the end of the study, patient loss in Diane and Androcur groups was 29.1% and 27.8%, respectively, and the mean percent difference in the scoring index was as follows: total, 24.6 Diane versus 30.8 Androcur, P less than 0.05; facial, 30.1 Diane versus 33.0 Androcur, P less than 0.10; bust, 12.1 Diane versus 31.2 Androcur, P less than 0.02; and abdomen, 20.1 Diane versus 31.2 Androcur, P less than 0.02. Except for breast tenderness (Diane greater than Androcur), amenorrhea, and weight gain, (Androcur greater than Diane), the incidence of side effects was comparable in both groups.

Adolescent↗

PubMed1985

Age-dependent, ovary-independent decrease in the nuclear binding kinetics of estrogen receptors in the brain of the C57BL/6J mouse.

To further define the role of aging of the brain in the induction of reproductive acyclicity, we put to death intact as well as castrated female C57BL/6J mice of various ages before and from 0.5 to 24 hours after subcutaneous injection of 0.2 micrograms of 17 beta-estradiol. Pooled hypothalamic and pituitary tissues were dissected and cytosolic/nuclear estrogen receptors were assayed in buffer that consisted of 10 mmol/L Tris(hydroxymethylaminomethane) hydrochloride, 1.5 mmol/L ethylenediaminetetraacetic acid, and 0.5 mmol/L dithiothreitol and contained molybdate (25 mmol/L) and inhibitors of proteases. Our results in intact animals indicated that baseline cytosolic concentration of estrogen receptors remained constant at 60 to 77 fmol/mg of protein (range) throughout aging, whereas nuclear levels of estrogen receptors decreased from 1.2 to 1.6 fmol/micrograms of deoxyribonucleic acid (range) to nondetectable levels after the onset of ovarian acyclicity. No age-related changes in the Ka were observed. After subcutaneous challenge with estrogen, nuclear binding of hypothalamic-pituitary axis estrogen receptors revealed a significant age-related decrease which was already evident at 10 to 14 months of age and prior to the onset of anestrous. Castration, whether performed neonatally or at 8 months of age, reduced the hypothalamic-pituitary axis concentration of estrogen receptors in middle-aged and aged animals, but did not prevent this blunted kinetics of nuclear binding. One week of daily injection of 17 beta-estradiol to intact and castrated mice of all age groups prior to binding kinetic studies induced maximal (five fold) increases in the content of hypothalamic-pituitary axis estrogen receptors in young animals which readily bound to the nucleus. After similar therapy to middle-aged and aged mice, minimal changes or even no changes were observed in both cellular estrogen receptor contents, despite similar increments in plasma levels of estrogen. These findings suggest an age-dependent decrease in the kinetics of hypothalamic-pituitary axis estrogen receptors manifested by a reduced synthesis of functional estrogen receptors in the brain of mice.

Aging↗

PubMed1985

Tubal infertility and the intrauterine device.

To study the association between intrauterine devices (IUDs) and pelvic inflammatory disease, we compared contraceptive histories in 4185 while women--283 nulliparous women with primary tubal infertility, 69 women with secondary tubal infertility, and 3833 women admitted for delivery at seven collaborating hospitals from 1981 to 1983. The relative risk of tubal infertility associated with IUD use was calculated by means of multivariate logistic regression to control for confounding factors, including region, year of menarche, religion, education, smoking, and reported number of sexual partners. The adjusted risk of primary tubal infertility associated with any IUD use before a first live birth was 2.0 (95 per cent confidence limits, 1.5 to 2.6) relative to nonuse. Users of the Dalkon Shield had an adjusted risk of 3.3 (1.7 to 6.1), users of the Lippes Loop or Saf-T-Coil had a risk of 2.9 (1.7 to 5.2), and users of copper IUDs had a risk of 1.6 (1.1 to 2.4). Women who reported having only one sexual partner had no increased risk of primary tubal infertility associated with IUD use. The adjusted risk of secondary tubal infertility associated with use of a copper IUD after a first live birth was not statistically significant (1.5; 95 per cent confidence limits, 0.8 to 3.0), whereas the risk from similar use of noncopper devices was significant (2.8; 1.3 to 5.9). We conclude that tubal infertility is associated with IUD use, but less so with copper IUDs.

Adult↗

PubMed1985

On the presence of nonfunctional uterine estrogen receptors in middle-aged and old C57BL/6J mice.

The nuclear binding kinetics of uterine 17 beta-estradiol (E2) receptors (UER) were studied throughout aging in intact and castrated (OVX) mice. When compared to young animals, 15- to 18-month-old mice showed a significant reduction in their total cytosolic (0.526 vs. 0.405 pmol/uterus; P less than 0.05) and nuclear (0.37 vs. 0.16 pmol/uterus; P less than 0.01) UER content, whereas the affinity (Ka) for estrogens remained constant (0.8-1.6 X 10(9) M-1). This age-related decrease in UER was preceded by a blunted and retarded nuclear binding of UER at 10-14 months of age, which was further accentuated after transition from perimenopause. Ovariectomy (OVX), whether performed neonatally or in adulthood, reduced the total concentration of cytosolic and nuclear UER in each age group studied, but did not prevent this reduced nuclear binding observed in middleaged mice. However, when standardized per tissue protein, the mean number of cytosolic UER from young and middle-aged, but not old, mice was reduced by 50% after neonatal OVX (176.5, 178.4, and 218.8 fmol/mg protein, respectively), whereas it remained unchanged when OVX was performed in adulthood and the animals subsequently studied at peri- and postmenopausal ages (326.3 and 283.3 fmol/mg protein, respectively). Daily administration of a physiological dose of E2 for 7 days to OVX mice of each age group induced maximal synthesis of UER in young animals, but not in peri- and postmenopausal ones; in peri- and postmenopausal animals, this was paralleled by reduced uterotropic responses despite similar increments in plasma E2. These results suggest an age-related, gonad-independent decline in the number of functional UER early in reproductive aging.

Aging↗

PubMed1985

Characterization of 3-hydroxy-3-methylglutaryl coenzyme A reductase in human adrenal cortex.

Our study compares the properties of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase from a human metastatic virilizing carcinoma and that from normal adrenal glands obtained from kidney donors. Optimal conditions for enzyme assay were obtained when a 50-mM imidazole buffer (pH 7.2) containing 5 mM EDTA, 250 mM NaCl, 1 mM phenyl-methylsulfonylfluoride, 0.1 mM leupeptin, and 5.5 mM dithiothreitol (DTT) was used. A 30-min preincubation period preceding addition of substrates enhanced reductase activity by 1.75-fold. In crude microsomal preparations, Km values were similar for both tumor and normal tissues and varied between 4 and 5 microM (S)HMG-CoA. The presence of NaF in homogenization and incubation media decreased the maximum velocity, but not the Km. A partially purified rat liver phosphorylase phosphatase preparation or a similar preparation from the carcinoma restored to maximal levels the reductase activity of microsomes prepared in the presence of NaF. A Km of 96 microM NADP was found for the carcinoma microsomal preparation. Preincubation of microsomes in the presence of monothioglycerol or DTT resulted in an increased reductase activity, suggesting a possible inactive enzyme precursor(s) consisting of disulfide-linked units. Reactions of the DTT-activated enzyme incubated in the presence of increasing amounts of NADPH showed sigmoidal kinetics. Under reducing conditions, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting revealed the presence of a 92.5K mol wt protein band that reacted with a rat antireductase antibody. Reductase activity in different regions of the carcinoma varied from 679-1763 pmol/mg protein, with an average of 1146 pmol. In three normal adrenal glands we found values of 23.4, 48.1, and 36 pmol. We concluded that the expression of HMG-CoA reductase activity was elevated in human adrenal carcinoma.

Adrenal Cortex↗

PubMed1984

Increased 3-hydroxy-3-methyl-glutaryl coenzyme A reductase activity in a virilizing adrenal carcinoma.

HMG-CoA reductase activity was determined on microsomal preparations of an adrenal carcinoma and on a control adrenal obtained from palliative surgery for breast carcinoma. In both tissues we also measured [14C]pyruvate incorporation to study the formation of sterols. The endogenous adrenal content of cholesterol and its esters was quantitated. The content of various steroids was also determined in tissues and media before and after incubations in Krebs-Ringer. The carcinoma had a HMG-CoA reductase activity of 972.0 pmol/mg protein/min vs 13.8 for the control adrenal. The tumor incorporated 4.6 pmol of [14C]pyruvate per mg protein per 90 min into digitonin precipitable sterols compared to 0.5 pmol found for the control gland. Free cholesterol and cholesterol esters in tumoral tissue were 0.09/100 mg and 0.02/100 mg tissue respectively, compared to 0.18 and 2.56 in control tissue. The output of corticosteroids and androgens was very high when calculated for the whole tumor. These results suggest that the carcinoma had acquired a high capacity for de novo synthesis of cholesterol which could have served as substrate for the observed high plasma androgen level.

Adrenal Cortex Hormones↗

PubMed1984

Luteinizing hormone-releasing hormone binds to enriched human placental membranes and stimulates in vitro the synthesis of bioactive human chorionic gonadotropin.

Partially purified cell membranes were prepared from midterm and term placentas after sedimentation on a sucrose density gradient. Biochemical characterization showed that the sucrose density pellet was enriched 8-fold in alkaline phosphatase activity and also contained the majority of [125I]LHRH binding sites. This enrichment was also confirmed by electron microscopy. Specific binding of LHRH was then determined by incubating iodinated LHRH or two of its superanalogs with increasing doses of the corresponding radioinert ligand. Scatchard representation of the data showed curvilinear plots whose first component revealed, for both stages of pregnancy, saturable binding of [125I]LHRH and its agonists with similar association constants (Ka) that ranged between 5.5 X 10(5) M-1 and 1.1 X 10(7) M-1. When standardized per milligram of DNA content, the number of binding sites ranged between 225 and 310 X 10(-12) M. Specificity was evidenced by the inability of a biologically active LHRH antagonist, oxytocin, and TRH to inhibit [125I]LHRH binding. Short term placental cultures incubated with 1.5 X 10(-6)M LHRH had increased production rates of both immunoassayable and bioassayable hCG, and this effect was 4-fold higher in midterm placental cultures. Placental incubations with either buffer or equimolar concentrations of oxytocin or TRH had no effect on hCG production. These observations expand information on extrapituitary binding sites of LHRH and suggest a role for this peptide in the physiology of the human placenta.

Cell Membrane↗

PubMed1984

Collaborative study of pregnancy rates following danazol therapy of stage I endometriosis.

Pregnancy rates following danazol therapy of endometriosis vary widely. In order to reduce variations in patient selection and establish danazol effectiveness, six collaborative centers evaluated 75 infertile patients with normal infertility screening studies and mild (stage I) endometriosis documented by laparoscopy. Following diagnosis and 3 months coital exposure, all patients were treated with danazol for 6 months, and patient surveillance after danazol therapy lasted at least 12 months, with a range of 12 to 34 months. Of the 75 patients treated, 21 (28%) conceived, and the term pregnancy rate was 20% (15 of 75). The low pregnancy rate observed in these patients suggests that the role of danazol therapy for patients with mild endometriosis and infertility should be reconsidered.

Adult↗

PubMed1983

Endocrine aging in C57 BL mice--II. Dynamics of estrogen receptors in the hypothalamic-pituitary axis.

Specific cytosolic and nuclear binding sites for estrogens were measured in the hypothalamic-pituitary axis (HPA) of young (4-8 months) and old (16-18 months) C57 BL mice in order to determine any age-related alteration in hormone-receptor interaction. Our results indicated no age differences in the affinity (KD = 0.89 +/- 0.03 (SEM) vs 1.09 +/- 0.2 X 10(-9) M), the specificity, the sedimentation profile (6 s) or in the number (98.9 +/- 4.9 vs 84.4 +/- 2.3 fmol/mg protein) of unoccupied estrogen binding sites in the cytosols. Estradiol administration to young mice induced a complete translocation of cytosolic estrogen receptors to the nucleus, and two types of nuclear binding sites were observed: Type I were specific for estrogens with high affinity (KD = 0.51 +/- 0.06 X 10(-9) M) and low binding capacity (115.1 +/- 22.7 fmol/mg DNA) and sedimented in the 4.0 s area, while Type II binding sites showed a much higher capacity and lower affinity for R2858. HPA nuclear suspensions of aged untreated mice showed undetectable (less than 50 fmol/mg DNA) levels of nuclear estrogen receptors and E2 pre-treatment resulted in a significant increase in both types of binding sites. While no significant changes in the physicochemical characteristics of these nuclear receptors were observed, when compared to young animals, aging was manifested by a translocation defect in the HPA of C57 BL mice. These results suggest aging changes in the endocrine regulating centers of the brain with defective activation of estrogen receptors.

Aging↗

PubMed1982

Endocrine aging in CBA mice: characterization of uterine cytosolic and nuclear sex steroid receptors.

We examined the evidence of alterations with age in sex steroid hormone/receptor interaction in the uteri of CBA mice. The mean affinity for estrogens and progesterone that we observed in uterine cytosols and nuclei of old (16-18 months) mice were no different than those observed in young (4-8 months) animals. Whereas the total number of unoccupied estrogenic receptor sites in old uteri did not differ significantly from that observed in uteri of young mice, aging was accompanied by a 3-fold and significant decrease in mean nuclear binding sites when standardized as mg of DNA (p less than 0.05). Contrary to estrogen receptors, aging uteri showed a 3-fold and significant decrease in the total number of uterine progesterone receptor concentration (p less than 0.05) which was manifested by a decrease of progesterone binding sites in both the cytosol and the nucleus. These results suggest that aging CBA mice present a profile of altered hormone-receptor interaction which is only partly dependent on ovarian steroids.

Aging↗

PubMed1982

Bromocriptine therapy in oligozoospermic infertile men.

A prospective, randomized double-blind study with crossover using bromocriptine and placebo was performed on a group of 17 infertile males with idiopathic oligozoospermia. Twelve patients completed the duration of this study of eight months by receiving 5 mg of bromocriptine per day for four months followed by four months of placebo or vice versa. Prior to treatment, the sperm count was 8.76 +/- 1.32 (10(6)/ml). The hormonal profile was performed prior to treatment and included estimation of prolactin, T3, T4, thyroid stimulating hormone (TSH), testosterone, follicle stimulating hormone (FSH), and plasma LH. Stimulation studies using LHRH and TRH were also performed. All hormonal estimations were within normal limits. Compared to placebo, bromocriptine had no significant effect on sperm analysis, or basic hormonal profile. The stimulation test with luteinizing hormone releasing hormone (LHRH) was unchanged except for the basic plasma testosterone, which increased. The prolactin decreased following the thyrotropin releasing hormone (TRH) stimulation. Two pregnancies were noted four to six weeks following the end of treatment. Bromocriptine did not seem to be more effective than placebo in the treatment of idiopathic oligozoospermia.

Adult↗

PubMed1981

Ovarian hyperthecosis: in vivo and in vitro correlations of the androgen profile.

A 36-year-old patient with secondary amenorrhea and progressive frank virilization was found by histologic examination to have ovarian hyperthecosis. Baseline androgenic investigation revealed a selective increase in testosterone (T) production rate (3.1 mg/day), which was associated with an increase in both plasma T concentration (total and unbound) and metabolic clearance rate (MCR) of T (2156 liters/day). There was a marked concentration gradient for circulating plasma T between each ovarian vein and the peripheral veins (right ovarian, 50 ng/ml; left ovarian, 21 ng/ml). After bilateral wedge resection there was a rapid decrease in the total and unbound T levels as well as in the MCR of T, which remained normal for at least 6 months. By then the patient had stopped shaving and was menstruating normally. In vitro incubation studies of fragments from each ovary revealed incorporation of [3H]-dehydroepiandrosterone and [3H]-progesterone into [3H]-T in the range reported for normal human ovarian stroma, and short-term cellular culture suggested a normal morphology and steroidogenesis. It is concluded that in this patient with ovarian hyperthecosis, the observed ovarian T production resulted more from an increase in the amount of stromal-thecal tissue than from a functional biochemical defect in the latter.

Adult↗

PubMed1980

The metabolism of androstenedione in human pregnancy: the use of constant infusion of unlabeled steroid to assess its metabolic clearance rate, its production rate, and its conversion into androgens and estrogens.

Using constant infusion of unlabeled steroid, we have studied the metabolic clearance rate (MCR), half-life (T 1/2), and conversion ratio of androstenedione (A) into androgens and estrogens throughout human pregnancy. In nonpregnant women, results obtained by infusion of unlabeled A were identical to those obtained by the infusion of either labeled steroid or a mixture of labeled and unlabeled steroid. A twofold increase in the infusion rate did not change any of these results, indicating that enzyme availability was not a limiting step. When compared to the nonpregnant state, pregnancy was associated with a twofold rise in plasma A production rate (PR) (p less than 0.05) but with minimal changes in its MCR or its T 1/2, thus leading to a twofold increase in the plasma concentration of A (p less than 0.05). The conversion of A into testosterone (T) rose twofold at term pregnancy (p less than 0.05), whereas that of A into estrone (E1) rose fivefold (p less than 0.01) and that of A into estradiol (E2) rose 16 fold (p less than 0.001). It is concluded that constant infusions of unlabeled A can be used successfully to study the kinetics of A when one is reluctant to infuse isotopic steroid.

Adult↗

PubMed1980

Adrenal androgen production in hyperprolactinemic states.

In order to better define the kinetics of the adrenal androgens in hyperprolactinemic states, we have studied 10 patients suspected of having a pituitary prolactinoma. Compared with the levels in 10 healthy control women (normal range: N), no significant differences in the mean (+/- standard error) plasma concentrations of cortisol (F), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DS), androstenedione (A), and testosterone (T) were found: F, 22.7 +/- 2.6 micrograms/100 ml (N = 10 to 25); DHEA, 7.5 +/- 1.4 ng/ml (N = 3.0 to 12.5); DS, 1.7 +/- 0.3 micrograms/ml (N = 1.1 to 3.6); A, 2.2 +/- 0.3 ng/ml (N = 0.5 to 3.5); T, 30.5 +/- 6.4 micrograms/100 ml (N = 20 to 80). Using constant infusions of unlabeled steroid, the metabolic clearance rates (MCR) of the adrenal androgens DHEA and DS were found to be 1282.6 +/- 342.6 liters/day and 5.6 +/- 1.4 liters/day, respectively, which were no different from the MRC of 1689.4 +/- 364.2 liters/day and 6.8 +/- 1.9 liters/day, respectively, found in the normal control women. Medical therapy with a dopaminergic agent in three of these patients reduced mean circulating levels of prolactin from 81.1 +/- 4.7 ng/ml to less than 15 ng/ml but did not change any of our results. It is concluded that, in the study group, hyperprolactinemia exerted minimal trophic effects on the production rates of adrenal androgens.

Adolescent↗