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Biomedical subjects

L Cedard

Publications and source records attributed to L Cedard.

At least 37 records · Page 2Linked to original sources

Androgen producing adrenal adenoma. Report on a case associated with hyperparathyroidism.

In a 41-year-old hirsute woman, severe hypercalcemia led to the discovery of hyperparathyroidism related to the involvement (hyperplasia/or adenoma) of the 4 parathyroid glands. Plasma and urinary DHA, plasma DHA-sulfate and delta 5 steroid precursors were elevated. Steroid hormone hypersecretion was stimulated by hCG and ACTH, and exhibited a paradoxical rise during dexamethasone administration. Computerized tomography scanning as well as arteriography disclosed bilateral adrenal hyperplasia and left adrenal adenoma. Bilateral adrenal vein catheterization indicated a left/right gradient for delta 5 steroids and delta 5 steroid sulfates. At surgery a left brown adrenal encapsulated adenoma was removed with a hyperplastic adrenal gland. Results of in vitro studies (adrenal steroid content and incubation) together with postadrenalectomy hormonal results suggest that the left brown adrenal adenoma was the main source of excessive androgen production. The infrequent association of an androgen-producing adrenal adenoma with hyperparathyroidism raises the hypothesis of multiple endocrine neoplasia syndrome. However, evidence for this diagnosis is lacking in the absence of other glandular involvement and of family history.

Adenoma↗

Prostaglandin E2-induced changes in the distribution of glycosaminoglycans in the isolated rat uterine cervix.

In order to study the hormonal control mechanisms of cervical ripening, we investigated the prostaglandin E2 (PGE2)-induced changes in the distribution of glycosaminoglycans (GAG) using hysterectomized and ovariectomized rats, leaving the vascularized uterine cervix in situ, as an animal model. In the first series of experiments, the GAG were measured in a control (n = 22 Wistar rats) and in a PGE2-treated group (n = 20 Wistar rats) without steroid supplementation. In the second series of experiments, the GAG were measured in a control (n = 19) and in a PGE2-treated group (n = 18) receiving estradiol and progesterone supplements. After PGE2 treatment in the two series of experiments, and despite being surgically isolated from the uterine corpus, the cervix was still able to undergo some of the structural changes associated with normal ripening (increased hydration and hyaluronic acid concentration). This suggests that PGE2, acting directly on the cervix, could be, at least in part, a modulator of biochemical events which underlie normal cervical maturation. The animal model described here seems to be suitable for studying the hormonal mechanisms of cervical ripening and the regulatory relationship between cervical maturation and myometrial contractility, which are probably subject to concordant endocrine regulation.

Animals↗

Progesterone and estradiol in saliva after in vitro fertilization and embryo transfer.

The importance of the luteal function to ensure adequate implantation prompted us to assay salivary estradiol (SE2) and salivary progesterone (SP) concentration serially after embryo transfer by simple and rapid radioimmunoassays to allow a noninvasive easily repeatable approach. SE2, which has fallen 1 day after human chorionic gonadotropin injection, increased after reimplantation (day 3), plateaued during approximately 1 week, and returned to basal levels before menstruation in absence of conception or in chemical pregnancy, whereas it increased steadily in successful pregnancy. SP increased in all the cases, formed a plateau, and returned progressively to basal levels before menstruation, whereas in ongoing pregnancy there was a transitory decline in the midluteal phase followed by a rapid and continuous increase, with a significantly higher ratio day 13/day 10 in successful pregnancy.

Adult↗

Incidence of placental sulfatase deficiency on the mode of termination of pregnancy.

The mode of termination of pregnancy in case of placental sulfatase deficiency (PSD) has been considered in a 28-case series from our laboratory. After comparison with 75 other cases collected from the literature and also with reports concerned with normal pregnancies it appears that in the case of PSD: first, the gestation length is not increased; second, the parity of the patients has no influence on the mode of delivery; third, spontaneous vaginal delivery can occur (67.8% in our series, 43% in the literature series); fourth, the failure rate of labor, especially when induced, is higher than in a normal population; fifth, the high rate of C-section, largely due to the failure of labor, is enhanced by untimely interventions mostly in case of isolated PSD. If a pejorative incidence of PSD on the mode of delivery exists it must be at a moderate level, and intervention is unnecessary in absence of associated fetal and/or maternal complications.

Amenorrhea↗

Effect of natural progesterone treatment during pregnancy on fetal testosterone and sexual behavior of the male offspring in the mouse.

The effect of maternal exposure to progesterone upon the fetal pituitary-gonadal axis and the sexual behavior of the male offspring of mice were studied. Daily injection of progesterone from days 14 to 16 of pregnancy reduced testosterone production in the fetus but caused a significant increase in circulating LH levels. Progesterone-exposed males showed no alteration in anogenital distance or in body weight at any time from birth to adulthood. At 80-90 days of age males from control and progesterone-exposed groups did not differ from each other in testis and seminal vesicle weights. However, in the latter group, there was a marked reduction in the percentage of males that displayed mount, intromission and ejaculation patterns. These findings indicate that in utero exposure to pharmacological doses of progesterone that do not cause abnormalities of male internal and external genitalia may interfere with masculine behavior in adulthood. This alteration could partially be due to diminished peripheral testosterone levels during the prenatal period.

Animals↗

Inhibin concentration in the culture media of human oocyte-cumulus-corona cell complexes is not related to subsequent embryo cleavage.

We have demonstrated an in vitro secretion of inhibin by human OCCC, not related to subsequent egg cleavage. A putative signal, released by OCCC, that could modulate inhibin secretion by granulosa cells has not been discovered. Inhibin secretion by OCCC has no predictive value concerning the further fertilization and cleavage of the oocytes.

Blastomeres↗

Detection of distinct receptors for native and acetylated low-density lipoproteins in human placental microvilli by ligand-immunoblotting.

Ligand-immunoblotting was used to detect distinct receptors for native low-density lipoprotein and for acetylated low-density lipoprotein on microvillous membranes from human term placentas. Antisera directed against native and modified low-density lipoproteins were prepared in rabbits and their specificities were assessed by immunodiffusion and immunoelectrophoresis. The receptor for low-density lipoprotein was detected as a 160 kDa protein and that for acetylated low-density lipoprotein as a 200 kDa protein. These receptors were compared with their counterparts in cultured human skin fibroblasts, bovine adrenal cortex and J774 macrophage-like cells. This is the first investigation that visualizes the presence of receptors for both native and modified low-density lipoproteins in a steroidogenic tissue.

Acetylation↗

Pregnancy-related changes in the distribution of glycosaminoglycans in the cervix and corpus of the human uterus.

We investigated the variations in the distribution of glycosaminoglycans (GAG) in the cervical, isthmic and corporeal stroma of the pregnant and non-pregnant human uterus. The GAG were measured in non-pregnant (n = 9) and pregnant (n = 14) cervices, in non-pregnant (n = 8) and pregnant (n = 6) uterine isthmus, and in non-pregnant (n = 12) and pregnant (n = 5) uterine corpus. Heparan sulfate is abundant in the isthmic and corporeal stroma. This has to be related to a larger content in blood vessels and muscular cells at this level than in the cervix. The distribution of hyaluronic acid and dermatan sulfate is the same in the cervix as in the corpus, but the amount of these GAGs is lower in the former, which could be due to a lower connective tissue content. Two of the main features of cervical maturation, increased hydration, and decreased dermatan sulfate concentration, were found also in the pregnant corporeal stroma. These results suggest that connective tissue maturation is not only a cervical phenomenon and could play a role in active and/or passive mechanical properties of the myometrium during late pregnancy and labor.

Adult↗

Identification of specific binding sites for acetylated low density lipoprotein in microvillous membranes from human placenta.

The ability of microvillous membranes isolated from human placenta to specifically bind human low density lipoprotein (LDL) modified by acetic anhydride has been investigated. The presence of saturable high affinity binding sites specific for [125I]acetyl-LDL was demonstrated. Scatchard analysis of the binding data, obtained at 4 degrees C, revealed a single class of sites with a mean KD value of 3.63 +/- 1.16 micrograms acetyl-LDL protein/ml, and a maximal binding capacity of 335.1 +/- 148.8 ng acetyl-LDL protein/mg of membrane protein. At 37 degrees C, the binding capacity was increased, while the KD value was not modified. The specificity of these binding sites was assessed by competition studies: unlabelled acetyl-LDL were effective competitors, whereas native LDL, VLDL and HDL3 were ineffective. Conversely, unlabelled acetyl-LDL failed to prevent the binding of native [125I]LDL to placental microvilli. The [125I]acetyl-LDL binding was partially inhibited (about 35%) by dextran sulfate and fucoidin, and was abolished by a pretreatment of the microvillous membranes with pronase. The binding sites specific for acetyl-LDL are present during all the gestation and are distinctly different from the binding sites for native LDL, previously characterized in placental microvilli. These 2 types of binding sites may be related to the high amount of cholesterol required by the human placenta for progesterone synthesis and trophoblastic growth.

Acetylation↗

Influence of the oral administration of micronized progesterone on plasma and tissue levels of steroids in human pregnancy.

A single dose of micronized progesterone, orally administered to women at different stages of pregnancy, induced an immediate increase in the plasma levels of progesterone. Progesterone was administered to another group of women just before elective cesarean section. Levels of progesterone, oestradiol-17 beta and oestrone were determined in plasma, placenta and at different sites of the myometrium obtained during the surgical procedure. Results were compared to those observed in a control group of women who did not receive progesterone. Progesterone levels demonstrated a marked increase in plasma and in the whole myometrium 150 min after administration; the levels then decreased rapidly to control values within one hour. The concentrations of progesterone in the placenta did not show any change. Evident modifications of the oestrogen levels appeared in the myometrium and in the placenta after the administration of progesterone whereas no change occurred in the plasma. No difference was observed in estradiol-17 beta in the myometrium whereas an increase was seen in the placenta. Estrone levels decreased in the myometrium and in the placenta. This study demonstrates a prompt delivery of an orally administered natural progesterone to the myometrial target tissue and subsequent modifications in the estrogen pattern. This provides a theoretical mechanism for the clinical use of progesterone in the prevention of premature labor.

Administration, Oral↗

Regulation of testosterone production in fetal testicular cells: effect of androgens.

Pre-incubation of dispersed testicular cells from 18-day-old mouse fetuses in presence of testosterone or dihydrotestosterone resulted in a significant decrease of the hCG-stimulated testosterone production. These results suggest that during late fetal life testosterone production may be inhibited by an ultra-short loop feedback of androgens.

Animals↗

Oral administration of micronized natural progesterone in late human pregnancy. Effects on progesterone and estrogen concentrations in the plasma, placenta, and myometrium.

A single dose of micronized oral progesterone was administered to 15 pregnant women immediately prior to elective cesarean section. Levels of progesterone, 17 beta-estradiol, and estrone were measured in the plasma, in the placenta, and at different sites in myometrium obtained during the surgical procedure. Results were compared to those observed in a control group of women who did not receive progesterone. Progesterone levels demonstrated a marked increase in plasma and in the whole myometrium 150 minutes after administration. The levels then decreased rapidly to control values in 1 hour. The concentrations of progesterone in the placenta did not show any changes. No difference appeared in 17 beta-estradiol levels in the plasma or the myometrium, whereas an increase was observed in the placenta. Estrone levels did not change in the plasma, but they decreased in the myometrium and in the placenta.

Administration, Oral↗

Radioimmunoassay of plasma and salivary progesterone during the menstrual cycle.

We have developed specific and sensitive radioimmunoassays for progesterone in saliva (SP4) easily applicable in routine practice to assess ovarian function. One of them uses [3H]progesterone, the other 3-CMO-[125I]histamine as tracer. The reliability criteria of both techniques have been controlled and the results obtained with the two methods in 50 saliva samples are correlated well. Our clinical study has been chiefly done with [3H]progesterone. In the present study we reported the values obtained daily during the greatest part of the menstrual cycle in 14 normal cases and they are in agreement with previous reports. The use of [125I]tracer, by increasing the sensitivity of the RIA and shortening the duration of the assay, improves the use of SP4 as a practical non-invasive sampling alternative for many clinical situations involving evaluation of the ovarian function.

Female↗

Hormonal regulation of testosterone production in short-term primary culture of fetal mouse Leydig cells.

Short-term primary culture of Leydig cells were prepared from 18 day old fetal mouse testes. The cells were cultured in a defined medium supplemented with 1% fetal calf serum, EGF and Insulin. The cells rapidly attached to the plastic culture dish. Seventy to eighty percent of the firmly attached cells stained positively for 3 beta-HSD activity and gradually assumed a flattened epitheloid appearance. The functional activity of these cells in terms of testosterone production and hCG-responsiveness was maintained for 2 days. There was a significant effect of plating density. Pre-culture (24 h) of fetal Leydig cells in the presence of 100 mIU hCG desensitized these cells to a subsequent stimulation by hCG. This is the first report of a short-term primary culture of fetal Leydig cells which demonstrates the maintenance of androgenic activity of these cells in vitro.

3-Hydroxysteroid Dehydrogenases↗

Low-density lipoprotein binding sites in the microvillous membranes of human placenta at different stages of gestation.

Microvillous membranes isolated from early gestation placentas (8-12 weeks of amenorrhoea) and from mid-term placentas (20-22 weeks of amenorrhoea) were used to study the specific binding of low-density lipoprotein (LDL) to the trophoblast. The purity of the microvillous preparations has been assessed by electron microscopy and by their enrichment in two membrane markers, 5'-nucleotidase and alkaline phosphatase. Evidence was presented demonstrating the existence of saturable binding sites for [125I]LDL in placental microvilli as early as 6 weeks of pregnancy. The apparent KD values for these binding sites have been determined by Scatchard analyses to be 6.98 +/- 0.83 and 6.57 +/- 0.81 micrograms protein LDL/ml, for early gestation and mid-term preparations, respectively. This apparent KD value was unaffected by a pretreatment of the membranes by heparin, as indicated by the mean values of 7.13 +/- 0.89 and 6.97 +/- 0.75 micrograms protein LDL/ml obtained for immature microvilli preincubated with or without heparin, respectively. Large variations of binding capacity were observed in each gestational age group and no significant difference was found between them. These results indicate that the LDL binding sites of the human placenta, located on the microvillous membranes, (i) are present as early as the 6th week of pregnancy, and (ii) display the same high affinity and specificity for LDL as those of the term trophoblast.

5'-Nucleotidase↗