Hormonal modulators of glial ABCA1 and apoE levels.

Apolipoprotein E (apoE) is the major lipid carrier in the central nervous system. As apoE plays a major role in the pathogenesis of Alzheimer disease (AD) and also mediates repair pathways after several forms of acute brain injury, modulating the expression, secretion, or function of apoE may provide potential therapeutic approaches for several neurological disorders. Here we show that progesterone and a synthetic progestin, lynestrenol, significantly induce apoE secretion from human CCF-STTG1 astrocytoma cells, whereas estrogens and the progesterone metabolite allopregnanolone have negligible effects. Intriguingly, lynestrenol also increases expression of the cholesterol transporter ABCA1 in CCF-STTG1 astrocytoma cells, primary murine glia, and immortalized murine astrocytes that express human apoE3. The progesterone receptor inhibitor RU486 attenuates the effect of progestins on apoE expression in CCF-STTG1 astrocytoma cells but has no effect on ABCA1 expression in all glial cell models tested, suggesting that the progesterone receptor (PR) may participate in apoE but does not affect ABCA1 regulation. These results suggest that selective reproductive steroid hormones have the potential to influence glial lipid homeostasis through liver X receptor-dependent and progesterone receptor-dependent pathways.

Gene expression signatures of breast tissue before and after cross-sex hormone therapy in female-to-male transsexuals.

OBJECTIVE: To evaluate gene expression signatures of breast tissue in female-to-male (FtM) transsexuals under cross-sex hormone therapy (HT). DESIGN: Prospective cohort study. SETTING: Academic research institution. PATIENT(S): Five hormone-naïve FtM transsexuals before and after HT. INTERVENTION(S): Breast tissue biopsy before and after 2 years of intramuscular testosterone undecanoate (1,000 mg every 12 wk) and oral lynestrenole (5 mg daily), and gene signature analysis by global gene expression array covering 28,869 genes. MAIN OUTCOME MEASURE(S): Differential regulation of specific genes and gene expression signatures. RESULT(S): We identified 2,250 differentially expressed probe sets. One hundred twenty probe sets showed >2-fold change, of which 77 (64.2%) were up-regulated and 43 (35.8%) down-regulated. Genes involved in transcription were most overrepresented, with 43 out of 97 (44.3%) annotated probes, e.g., the transcription factor complex activator protein 1, including all three Jun genes (c-Jun, JunB, and JunD), two Fos genes (c-Fos and FosB), and activating transcription factor 3. In a Database for Annotation, Visualization, and Integrated Discovery analysis of the 2,007 down-regulated probe sets, proteins of the ribosome pathway and of two pathways involved in protein degradation, i.e., proteasome- and ubiquitin-mediated proteolysis, were significantly down-regulated. We identified eight breast cancer-associated gene expression signatures significantly overlapping with differentially regulated probe sets after cross-sex HT. CONCLUSION(S): Cross-sex HT in FtM transsexuals leads to the up-regulation and down-regulation of 243 and 2,007 distinct genes, respectively, and is associated with breast cancer-related gene expression signatures.

[State of the hypothalamo-hypophyseal-ovarian system in young nullipara women with ectopia of the cervix of uterus during taking the hormonal contraceptives].

Background diseases of the cervix of the uterus play one of the leading roles in the structure of gynecological pathology and present the risk of the development precancerous changes. Ectopia is observed in the structure of precancerous processes of the cervix of the uterus in 38, 8% of women and in 42, 2% cases of gynecological diseases. Our aim is to investigate the content of gonadotropic and steroid hormones in the blood plasma of young nullipara women with different types of ectopia during taking hormonal contraceptives. Cohort study has been carried out by using simple blind method. The quantitative data analyses were performed using the Statistical Package for the Social Sciences (SPSS) in order to reveal the correlation between taking of oral hormonal contraceptives and the hormone content in the blood plasma among young nullipara women with different types of ectopia. Descriptive statistics were calculated for all the study variables. The results displayed correlation between taking the oral hormonal contraceptives and changes of hormonal background in young women with ectopia of the cervix of the uterus during taking hormonal contraceptives. The study show that the secretions of gonadotropic hormone and ovary hormone peculiarities depend on the type of ectopia of the cervix of the uterus. The effect of hormonal contraception on cervix of the uterus of young nullipara women with ectopia was investigated. The oral contraceptive, Exluton is recommended in young nullipara women with ectopia.

Birth control pills and nonprofessional voice: acoustic analyses.

PURPOSE: Two studies are presented here. Study 1 was aimed at evaluating whether the voice characteristics of women who use birth control pills that contain different progestins differ from the voice characteristics of a control group. Study 2 presents a meta-analysis that combined the results of Study 1 with those from 3 recent studies that compared voices of women who use and do not use birth control pills. METHOD: In Study 1, voice samples from 30 women with no history of voice training, who use pills with different progestins (drospirenone, desogestrel, gestodene), and 10 women who do not use the pill were recorded at specific time points across the menstrual cycle and were analyzed acoustically. In Study 2, results from Study 1 were analyzed jointly with results from three recent studies, which used similar methodologies. RESULTS: Results of Study 1 did not reveal acoustic differences in sustained phonation of vowels across the pill groups and controls. Results of the meta-analysis performed in Study 2 indicated that pill users exhibited lower jitter and shimmer values on sustained vowels, whereas no difference of fundamental frequency was observed among women who use the pill. CONCLUSIONS: These results support findings from previous studies, which suggested that no adverse effect on voice was detected among nonprofessional speakers who use new-generation monophasic birth control pills, for the measures studied. Furthermore, results of the meta-analysis suggested that some acoustic properties of the voice, which are reflected in perturbation measures in sustained vowels, may be improved among women who use the pill.

In vivo induction of sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) by lynestrenol.

Genotoxicity study of synthetic progestin lynestrenol, was carried out on mouse bone marrow cells using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) as parameters. Lynestrenol was studied at three different doses (6.87, 13.75 and 27.50 mg/kg body wt.). SCE and CA increased significantly as compared to normal control when treated with lynestrenol at 13.75 and 27.50 mg/kg body wt. The present results suggest that lynestrenol has both a genotoxic and cytotoxic effects in mouse bone marrow cells.

A 3-year double-blind, randomized, controlled study on the influence of two oral contraceptives containing either 20 microg or 30 microg ethinylestradiol in combination with levonorgestrel on bone mineral density.

In this first prospective, double-blind, randomized, parallel-group study we evaluated the influence of two combined oral contraceptives on bone mineral density (BMD) and metabolic bone parameters. One dose-reduced preparation contained 20 microg ethinylestradiol (EE) in combination with 100 microg levonorgestrel (LNG) (20/100) was compared with the reference preparation which contained 30 microg EE in combination with 150 microg LNG (30/150). Data from 48 volunteers aged 20-35 years were obtained over an observation period of 36 treatment cycles. The direction of the change (increase or decrease) in all investigated bone-related variables was similar in both treatment groups. As compared to baseline, bone mineral density decreased by 0.4% in the 20/100 group and by 0.8% in the 30/150 group after 36 treatment cycles. These changes were not significantly different between the two treatment groups (p = 0.902). For bone-specific alkaline phosphatase, we measured a mean increase of 55.4% (20/100 group) and of 113.2% (30/150 group) after 36 treatment cycles. The two treatments did not differ statistically significantly (p = 0.522). With respect to cross-linked N-telopeptides (NTx), we detected a decrease of the mean NTx urine concentrations of 21.1% (20/100) and of 13.4% (30/150). These changes also did not significantly differ between the two treatments (p = 0.613). Both study treatments were safe and well-tolerated by all volunteers participating in the study. In conclusion, BMD did not change during the 3-year observation period. Thus, both trial preparations containing either 20 or 30 microg EE in combination with LNG were capable of maintaining BMD in young fertile women. There is no reason to assume that the EE dose reduction had any negative impact on BMD. Because there were no differences in BMD between the treatment groups, it can be assumed that even lower dosages than 20 microg EE might be sufficient for bone protection. Biochemical markers provided evidence for a reduced bone resorption.

The effect of ethinyloestradiol and levonorgestrel on the CYP2C19-mediated metabolism of omeprazole in healthy female subjects.

AIMS: To study the effect of an oral contraceptive (OC) formulation containing ethinyloestradiol and levonorgestrel (LNG) (combination OC) or LNG alone on the CYP2C19-mediated hydroxylation of omeprazole in healthy females. METHODS: This was an open crossover study with three phases. In phase one, 10 healthy females received a single 40-mg dose of omeprazole. Thereafter the subjects received in a random order either 40 micro g ethinyloestradiol and 75 micro g LNG or 60 micro g LNG alone once daily for 10 days. On day 10, 1 h after the last OC dose, subjects received a single 40-mg oral dose of omeprazole. The plasma concentrations of omeprazole, 5'-hydroxyomeprazole and omeprazole sulphone were determined for up to 8 h. RESULTS: The use of combination OC increased the area under the curve (AUC) of omeprazole by 38% [95% confidence interval (CI) - 3.8, 80; P = 0.040] and caused a 48% increase (95% CI 28, 68) in the AUC ratio of omeprazole/5-hydroxyomeprazole. LNG alone did not effect the 5'-hydroxylation of omeprazole. Neither of the OC preparations seemed to have an inhibitory effect on the formation of omeprazole sulphone by CYP3A4. CONCLUSIONS: Oral contraceptives containing ethinyloestradiol but not those containing only LNG decrease CYP2C19 activity.

FSH and ovarian response: spontaneous recovery of pituitary-ovarian activity during the pill-free period vs. exogenous recombinant FSH during high-dose combined oral contraceptives.

OBJECTIVE: Compare spontaneous recovery of pituitary-ovarian activity during the pill-free period following the correct use of low-dose oral contraceptives and subsequent ovarian function during the administration of exogenous recombinant FSH (recFSH) after switching to continued Lyndiol (2.5 mg lynestrenol + 0.05 mg ethinyl-oestradiol) medication. DESIGN: Prospective, randomized, group-comparative, single-centre study. Following the monitoring of the pill-free period (week 1) and subsequent treatment with Lyndiol (for a total of 5 weeks), all subjects were randomly allocated to one of four groups receiving daily FSH injections for 1 week [75, 150, 225 IU recFSH or 150 IU purified urinary FSH (uFSH)] during the fourth week of Lyndiol use. PATIENTS: Thirty-six healthy volunteers aged 18-39 years, prestudy oral contraceptive use for at least 3 months, cycle length between 24 and 35 days. MEASUREMENTS: Serum FSH, LH and oestradiol (E2) concentrations as well as transvaginal ultrasound assessment of the number and diameter of follicles > 2 mm were used to monitor pituitary ovarian function. RESULTS: At the start of the pill-free period following the prestudy contraceptive medication, 67% of the women presented with LH and FSH levels < 1 IU/l and only one follicle > 10 mm was observed. Initial levels of LH and FSH correlated (P < 0.05) with the extent of pituitary-ovarian activity during the pill-free period. At the end of the pill-free period a follicle > 10 mm had emerged in one subject only. During the first 3 days of Lyndiol use, seven women (19%) eventually showed at least one follicle > 10 mm. During combined exogenous FSH and Lyndiol administration, LH levels remained completely suppressed (< or = 0.5 IU/l) in all women studied. FSH levels and number and size of follicles increased with increasing doses of exogenous FSH in a dose-dependent manner. E2 levels remained low in all groups (< 150 pmol/l). During the week following FSH administration, FSH levels and E2 levels decreased gradually while the number of follicles > 10 mm still increased. CONCLUSIONS: We have confirmed that dominant follicles > 10 mm are present at the end of the pill-free period and during the first days after resumption of pill intake. Once follicles > 10 mm arose at the end of the pill-free period, continued use of Lyndiol did not reduce follicle diameters. One week of Lyndiol reduces pituitary-ovarian activity to levels observed after 3 weeks of low-dose pills. FSH administration during Lyndiol resulted in dose-dependent follicle growth despite extremely low LH levels. E2 secretion (56 +/- 51 pmol/l) occurred to a limited and variable extent along with extremely low serum LH concentrations. Recovery of pituitary-ovarian activity at the end of the pill-free period is comparable to FSH levels and follicle dynamics following 7 days of 75-150 IU/l recFSH.

Modulatory influence of oral contraceptives on mammary growth pattern of normal and ovariectomised mice.

The present study reports the modulatory influence of oral contraceptive formulations, Ovral (0.05 mg ethinylestradiol plus 0.5 mg norgestrel per pill), Noracycline (0.05 mg ethinylestradiol plus 0.1 mg lynestrenol per pill), Pearl (0.03 mg ethinylestradiol plus 0.30 mg norgestrel) and Centchroman (30 mg), on the growth and developmental pattern of murine mammary epithelium in normal as well as ovariectomised mice. Oral treatments of ovariectomised mice for 15 days with doses D1 (1/5th of a pill) and D2 (1/10th of a pill) of Ovral, Noracycline and Pearl enhanced the diameter of the terminal end buds (TEBS) and lateral buds (LBS) significantly. The increase in the diameters of TEBS and LBS on treatment with similar doses of Centchroman were not much significant. Hence, it may be concluded from the present study that the growth and development pattern of mammary epithelium can be modulated by treatment with oral contraceptives Oral, Noracycline, Pearl and Centchroman which is indicated by the increase in the diameters of TEBS and LBS.

PIP: In India, researchers at Jawahar Lal Nehru University in New Delhi compared data on 80 bilaterally ovariectomized 4-5 week old virgin mice with data on 10 nonovariectomized age- and sex-matched controls to examine the modulatory influence of various combined oral contraceptives (OCs) on the growth and developmental pattern of mammary epithelium. The experimental groups of 10 mice each received either 20% or 10% of an OC pill administered orally for 15 days. The OC formulations included Ovral (.05 mg ethinyl estradiol [EE2]+ .5 mg norgestrel), Noracycline (.05 mg EE2 + .1 lynestrenol), Pearl (.03 EE2 + .3 norgestrel), and Centchroman (a nonsteroidal contraceptive, 30 mg). Ovral, Noracycline, and Pearl at both doses increased the diameter of the terminal end buds and lateral buds of ovariectomized and nonovariectomized mice (p .0000001). Even though Centchroman also enhanced the diameter of the terminal end buds and lateral buds, the increase was not significant. These findings show that combined OCs do modulate the growth and developmental pattern of mammary epithelium. They lead us to question whether OCs might also increase the risk of breast cancer. In fact, many epidemiological studies demonstrate an increase in the risk of breast cancer among OC users.

Antiandrogen treatment with spironolactone and linestrenol decreases bone mineral density in eumenorrhoeic women with androgen excess.

Increased bone mineral density (BMD) has been reported in young women with androgen excess. To determine whether antiandrogen treatment in young women with androgen excess reduces BMD in these patients, the authors measured BMD before and a year after the beginning of antiandrogen therapy with spironolactone and linestrenol in 17 consecutive androgenized patients (median age 22 years). After a year's treatment BMD declined in 15 out of 17 patients, the mean decrease--0.032 g/cm2 (95% CI of the difference 0.016-0.048)--being highly significant (p < 0.001). Androstenedione decrease was the only hormonal variable significantly correlating with BMD decrease (r = 0.5; p = 0.037) according to simple linear regression. A decrease of BMD might become a key factor in deciding about the duration of antiandrogen treatment with spironolactone in functional hyperandrogenemia.

Effects of oral contraceptive pills on drug metabolizing enzymes and acid soluble sulfhydryl level in mouse liver.

The present paper reports the modulatory influence of two widely used combined oral contraceptive pills "OVRAL" and "NORACYCLINE" on hepatic phase I and II drug metabolizing enzymes and acid soluble sulfhydryl group of the mouse. Three different doses of the pills were used in this study i.e. D1 (1/2000th of a pill), D2 (1/200th of a pill) and D3 (1/20th of a pill). The sulfhydryl group increased significantly with the D1 and D2 dose of Ovral and the D2 dose of Noracycline. Dose D2 of both pills decreased cyt.P450 and cyt.b5 contents. D3 of Noracycline, however increased both the cytochrome levels. Dose D3 of Ovral and all three doses of Noracycline reduced the glutathione S-transferase activity.

Progestin treatment depresses estrogen receptor but not cathepsin D levels in needle aspirates of benign breast disease.

We studied the effect of a progestin (lynestrenol) on estrogen receptors (ER) and cathepsin D (cath-D) levels immunochemically in successive fine needle aspirates of benign breast disease. Fibrocystic disease was the main pathology (43 out of 47 patients). Thirty-one patients were treated with 10 mg of lynestrenol daily from the fifth to the twenty-fifth day of the menstrual cycle for 1 to 3 months. Sixteen untreated patients were used as controls. Lynestrenol significantly decreased the percentage of ER stained cells. This is in agreement with the antiestrogenic effect of progestin and, for the first time, indicates that in vivo progestin may decrease the stimulatory effect of estrogens on mammary cells by decreasing their estrogen receptor content. No effect of progestin on cath-D level was found throughout the whole population. However, this level varied more between aspirates of each patient in the treated group than in the control group, suggesting heterogeneity in patient responses to progestin. Since cath-D may have a role in carcinogenesis, clinical follow-up of these patients and more detailed studies are required to determine whether this progestin-challenge test has any value for detecting high risk mastopathies and for predicting effectiveness of treatment.

Serum lipids and lipoproteins during therapeutic amenorrhea induced by lynestrenol and depot-medroxyprogesterone acetate.

Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B) were determined in mentally handicapped subjects (n = 87). 33 women were on lynestrenol 5-10 mg for therapeutic amenorrhea (TA). 18 of them were randomly allocated to continue on lynestrenol and 15 were switched to intramuscular administration of medroxyprogesterone (DMPA). The switch to DMPA resulted in significant increases in HDL-C (33%), Apo A1 (12%), as well as in the HDL-C/LDL-C (48%) and Apo A1/Apo B (22%) ratios. The concentrations of HDL-C and Apo A1 were significantly greater in patients receiving DMPA, than in patients continuing with lynestrenol therapy. The amenorrhea incidence, however, did not differ between the two therapy groups. It is concluded that therapy with DMPA may be associated with smaller atherosclerosis risk than with peroral lynestrenol, because of its weaker effect on HDL-C and A1 levels.

[Compared action of norethindrone and various steroids on Müller ducts of the female chick embryo]. / Action comparée de la noréthindrone et de divers stéroïdes sur les canaux de Müller de l'embryon femelle de Poulet.

Treatment of female chick embryo with norethindrone (NET), a potent progesterone-like steroid, caused caudal agenesia and cephalic regression of Mullerian ducts as the normal regression induced by anti-Mullerian-hormone in the male embryo. The comparative study of five other progesterone-like steroids shows that only lynestrenol which is metabolized into NET at least in man, possesses the same properties as NET. The four others, i.e. medroxyprogesterone, medrogestone, norgestrienone and 17 alpha hydroxyprogesterone are only able to induce agenesia, an unspecific property, which was observed with many steroidal hormones, as norethandrolone here studied.

Prostaglandins: PGF2 alpha, PGE2, 6-keto-PGF1 alpha and TXB2 serum levels in dysmenorrheic adolescents before, during and after treatment with oral contraceptives.

Ten adolescents with primary dysmenorrhea (PD) were treated with the oral contraceptive (OC) Lyndiol 2.5 mg (R) for one cycle. The levels of PGF2 alpha, PGE2 and the metabolites of PGI2 and TXA2: 6-keto-PGF1 alpha and TXB2 were tested by a radioimmunoassay method during the 1st and 23rd day of the pre-treatment cycle (PrTC), the 23rd day of treatment (TC) and the 1st day of the post-treatment cycle (PoTC). The ratios PGF2 alpha/PGE2 and TXB2/6-keto-PGF1 alpha were also tested and compared during the above-mentioned days. Analytical comparison was made, for each Prostaglandin (PG) separately, between the 1st day of the PrTC and PoTC as well as the 23rd day of the PrTC and TC, respectively. All PG levels during TC and PoTC were found significantly lower, compared to those of the PrTC respectively. With regard to the ratios mentioned above, no statistically significant differences were found on the same days and cycles as previously stated. The reduction of the PG levels in PD patients after treatment with oral contraceptives, together with an improvement of the clinical findings of the disease, support the theory that oral contraceptives can be used for the treatment of PD cases, especially for those adolescents who also desire a contraceptive method.

The effect of peroral lynestrenol on serum lipids and lipoproteins in therapeutic amenorrhea of mentally retarded women.

Serum concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), and triglyceride (TG) were measured and that of low density lipoprotein cholesterol (LDL-C) calculated in blood samples obtained from mentally handicapped women undergoing therapeutic amenorrhea (TA) induced by 5-10 mg of peroral lynestrenol, some receiving, some not receiving simultaneous anticonvulsant therapy (phenytoin, carbamazepine or barbiturate, alone or in combination). In addition, these analyses were carried out in women receiving only anti-convulsants and in controls (mentally handicapped women not receiving any of the above-mentioned medications). Significantly lower HDL-C, Apo A1, TG and cholesterol concentrations were measured in TA patients receiving lynestrenol only, than in those receiving anticonvulsants only, or in controls (p less than 0.001). With regard to HDL-C and Apo A1, patients receiving both lynestrenol and anticonvulsants were intermediate between lynestrenol only patients and controls, but the HDL-C/LDL-C and Apo A1/Apo B ratios were similar to those observed in lynestrenol only patients. Addition of 8 or 12 mg of estriol succinate to the lynestrenol regimen was virtually without an effect. However, halving of the lynestrenol dose resulted in a significant increase in HDL-C and in the HDL-C/LDL-C and Apo A1/Apo B ratios (p less than 0.001 or p less than 0.01), respectively. The lynestrenol dose was thus the most important determinant of lipoprotein pattern and should be kept as small as possible in order to reduce cardiovascular risk.

[Is the progesterone test a generalizable method of screening for neoplastic and preneoplastic lesions of the endometrium?]. / Le "test à la progestérone" est-il la méthode généralisable de dépistage des lésions néoplasiques et prénéoplasiques de l'endomètre?

A "progesterone test" has recently been proposed as a tentative method to detect early neoplastic and pre-neoplastic lesions of the uterus endometrium. At the time progesterone is stopped, a "deprivation" metrorragia demonstrates a remanent hyperoestrogenism, which represents a well-known risk factor for this type of lesion. The method has been evaluated in private practice; 389 patients were offered the test: 87% accepted. Metrorragias were observed in 28% of the cases; however, no neoplastic nor pre-neoplastic lesions could be detected in this group of patients. Moreover, one patient presented with an advanced endometrial cancer one year after a negative test. The reliability of such a test clearly needs further evaluation.

Progestogen addition during oestrogen replacement therapy--effects on vasomotor symptoms and mood.

Vasomotor symptoms and mood changes were followed in 2 groups of post-menopausal women receiving cyclic replacement therapy with 3 mg/day of percutaneous oestradiol-17 beta alone or in sequential combination (days 11-21) with lynestrenol 5 mg/day. During 6 mth of therapy, daily symptom ratings were performed using a visual analogue scale technique. Serum levels of oestradiol were similar in both groups but sequential oestrogen/progestogen treatment was more efficient in suppressing vasomotor symptoms and serum gonadotropins. However, all negative mood symptoms were also more pronounced in this group. Progestogen addition may enhance the therapeutic effect on hot flushes and sweats but, at least in individual women cause unfavourable effects on mental status, mood and well-being.

Hormonal contraceptive increases plasma lipid peroxides in female rats. Relationship to platelet aggregation and lipid biosynthesis.

We investigated whether changes in plasma oxidative properties could occur after oral (hormonal) contraceptive (OC) administration in female rats and whether such changes could be responsible for the platelet increase in aggregation and lipid biosynthesis observed with that treatment. Platelets and plasma (platelet-poor) from control and OC (ethinyl estradiol + lynestrenol)-treated rats were prepared separately. Thrombin-induced aggregation of control platelets was markedly enhanced after incubation for 4 (p less than 0.025) to 60 (p less than 0.001) minutes in OC as compared with control plasma. Under the same conditions, platelet lipid biosynthesis was increased also (p less than 0.05 to p less than 0.01), but after 3 hours incubation. The enhanced response of platelets to aggregation induced by OC plasma could be inhibited by adding either glutathione (p less than 0.025), vitamin E (p less than 0.025), catalase (p less than 0.05), or peroxidase + glutathione (p less than 0.005) to plasma or 2,6,di-bis(ter-butyl)p-cresol (p less than 0.05) to platelets before incubation. The peroxidized free fatty acids isolated from OC plasma added to normal platelets induced a 150% (p less than 0.001) increase in the response to thrombin as compared with the fatty acids from control plasma. In addition, the level of malondialdehyde and conjugated dienes was significantly (p less than 0.02 to p less than 0.001) increased in OC compared with control plasma. We conclude that the enhanced formation in plasma of lipid hydroperoxides seems to be the initial event stimulating platelets after OC treatment, at least in rats.

Induction of estradiol dehydrogenase activity in human uterine endometrium by synthetic steroids.

The effects of P and six synthetic steroids (MPA, ENT, CAP, R2323, DL and EEL) on estradiol dehydrogenase (E2DH) activity were studied in normal human uterine endometrium in vitro. The mean value of E2DH activity in the proliferative endometrium was 1.5 +/- 0.2 nmol/mg protein/h and that in the secretory endometrium was 10.2 +/- 1.1 nmol/mg protein/h. There was a 7-fold increase in the secretory phase. E2DH activity in the uterine endometrium was stable during the culture period of up to 72 h. In the proliferative endometrium, P, MPA and ENT (approximately 10(-6)M) induced E2DH activity during a 24-h incubation. CAP and R2323 had no significant effect. EEL and DL had negligible effects. In contrast, E2DH activity in the secretory endometrium was not induced further by the steroids. Therefore, in the proliferative endometrium, the elevation of E2DH activity is attributable to the progestational activity and, in the secretory endometrium, E2DH activity is not increased further by the progestational agents because it has been already activated fully by P.