Rise In Estrogen Research Articles

Molecular and Functional Signature of Heart Hypertrophy During Pregnancy

During pregnancy, the heart develops a reversible physiological hypertrophic growth in response to mechanical stress and increased cardiac output; however, underlying molecular mechanisms remain unknown. Here, we investigated pregnancy-related changes in heart structure, function, and gene expression of known markers of pathological hypertrophy and cell stretching in mice hearts. In late pregnancy, hearts show eccentric hypertrophy, as expected for a response to volume overload, with normal left ventricular diastolic function and a moderate reduction in systolic function. Pregnancy-related physiological heart hypertrophy does not induce expression changes of known markers of pathological hypertrophy like: alpha- and beta-myosin heavy chain, atrial natriuretic factor, phospholamban, and sarcoplasmic reticulum Ca2+-ATPase. Instead, it induces the remodeling of Kv4.3 channel and increased c-Src tyrosine kinase activity, a stretch-responsive kinase. Cardiac Kv4.3 channel gene expression was downregulated by approximately 3- to 5-fold, both at the mRNA and protein levels, and was paralleled by a reduction in transient outward K+ currents, a longer action potential and by prolongation of the QT interval. Downregulation of cardiac Kv4.3 transcripts was mimicked by estrogen treatment in ovariectomized mice, and was prevented by the estrogen receptor antagonist ICI 182,780. c-Src activity increased by approximately 2-fold in late pregnancy and after estrogen treatment. We propose that, in addition to mechanical stress, the rise of estrogen toward the end of pregnancy contributes to pregnancy-related heart hypertrophy by increased c-Src activity and that the rise of estrogen is one factor that down regulates cardiac Kv4.3 gene expression providing a molecular correlate for a longer QT interval in pregnancy.

The effect of the steroid sex hormones on the nasal airway during the normal menstrual cycle

Problem: The changes in the nasal mucosa during the female menstrual cycle have been little researched and the role of oestrogens debated. The aim of this study was to measure a spectrum of physiological parameters in relation to the peak and trough of these hormonal levels. Methods: Ten women underwent measurements at the onset of menses and at the time of ovulation. On each occasion, anterior rhinoscopy, peak inspiratory nasal flow, acoustic rhinometry, anterior rhinomanometry, mucociliary clearance time, and rhinitis questionnaire score were recorded. Results: All measurements except anterior rhinoscopy showed a difference between the 2 readings consistent with nasal congestion at the peri-ovulatory stage of the cycle, of which anterior rhinomanometry and mucociliary time were significant ( P < 0.05). Conclusion: Nasal congestion therefore occurs in conjunction with the rise in serum oestrogens that occur at ovulation in the normal menstrual cycle. Significance: Pharmacological antagonism of oestrogens may therefore relieve nasal congestion and is currently under further research. Support: None reported.

Sex Differences in Knee Joint Laxity Change Across the Female Menstrual Cycle

To elucidate the hormonal influences on sex differences in knee joint behavior, normal-menstruating females were compared to males on serum hormone levels and anterior knee joint laxity (displacement at 46N, 89N and 133N) and stiffness (Linear slope of deltaForce/deltaDisplacement for 46-89N and 89-133N) across the female menstrual cycle.Twenty-two females were tested daily across one complete menstrual cycle, and 20 males were tested once per week for 4 weeks. Five days each representing the hormonal milieu for menses, the initial estrogen rise near ovulation, and the early and late luteal phases (total of 20 days) were compared to the average value obtained from males across their 4 test days.Sex differences in knee laxity were menstrual cycle dependent, coinciding with significant elevations in estradiol levels. Females had greater laxity than males on day 5 of menses, days 3-5 near ovulation, days 1-4 of the early luteal phase and days 1, 2, 4 and 5 of the late luteal phases. Within females, knee laxity was greater on day 5 near ovulation compared to day 3 of menses, and days 1-3 of the early luteal phase compared to all days of menses and day 1 near ovulation. On average, differences observed between sexes were greater than those within females across their cycle. There were no differences in anterior knee stiffness between sexes or within females across days of the menstrual cycle.

The effect of the steroid sex hormones on the nasal airway during the normal menstrual cycle.

The changes in the nasal mucosa during the menstrual cycle have been little researched and the role of oestrogens debated. The aim of this study was to measure a spectrum of physiological parameters in relation to the peak and trough of these hormonal levels. Ten women underwent measurements at the onset of menses and at the time of ovulation. On each occasion, anterior rhinoscopy, peak inspiratory nasal flow, acoustic rhinometry, anterior rhinomanometry, mucociliary clearance time and rhinitis questionnaire score were recorded. All measurements except anterior rhinoscopy showed a difference between the two readings consistent with nasal congestion at the peri-ovulatory stage of the cycle, of which anterior rhinomanometry and mucociliary time were significant (P <or= 0.05). Nasal congestion therefore occurs in conjunction with the rise in serum oestrogens that occur at ovulation in the normal menstrual cycle. Pharmacological antagonism of oestrogens may therefore relieve nasal congestion and is currently under further research.

Mechanisms of labour--biochemical aspects.

The mechanism of labour is not fully understood and further research into this important physiological process is needed. In some species, notably sheep, parturition is due to activation of the fetal hypothalamic-pituitary-adrenal axis. However, in primates, this axis appears to have a supportive, rather than essential role. Successful parturition requires an increase in coordinated uterine contractility together with changes in connective tissue that allow cervical ripening and dilatation. In most mammals, however, these changes are synchronised by a fall in maternal progesterone levels and a rise in oestrogens. This is not the case in women in whom the onset of labour occurs without apparent changes in circulating steroid levels. The basis of uterine contractility is the interaction between actin and myosin in myometrial smooth muscle cells. This is driven by calcium through Ca(2+)-calmodulin-dependent myosin light chain kinase (MLCK) activity. Moreover, calcium sensitisation occurs via activation of Rho kinase, a calcium-independent pathway that promotes contractility by inhibiting myosin phosphatase and probably by phosphorylating myosin on the same site as MLCK. Uterine activity can be modulated by many G-protein coupled receptors (GPCRs). For example, receptors coupled to Galpha(q) (oxytocin-, prostanoid FP and TP, endothelin-receptors) stimulate contractility by activating the phospholipase C/Ca(2+) pathway; receptors coupled to Galpha(s) (beta(2)-adrenoceptors, prostanoid EP2 and IP, some 5-hydroxytryptamine receptors e.g. 5-HT(7)) relax the uterus by increasing myometrial cyclic AMP levels; and receptors coupled to Galpha(i) (alpha(2)-adrenoceptors, muscarinic, 5-HT(1)) potentiate contractility, probably by inhibiting cAMP production. Because of its relative abundance in pregnant uterine tissue, the oxytocin receptor is an obvious target for tocolytic therapy. Oxytocin antagonists have been introduced into clinical practice for the management of preterm labour and offer the advantage of uterine selectivity and fewer side effects than conventional beta-agonist therapy.

Mechanisms of labour—biochemical aspects

The mechanism of labour is not fully understood and further research into this important physiological process is needed. In some species, notably sheep, parturition is due to activation of the fetal hypothalamic–pituitary–adrenal axis. However, in primates, this axis appears to have a supportive, rather than essential role. Successful parturition requires an increase in coordinated uterine contractility together with changes in connective tissue that allow cervical ripening and dilatation. In most mammals, however, these changes are synchronised by a fall in maternal progesterone levels and a rise in oestrogens. This is not the case in women in whom the onset of labour occurs without apparent changes in circulating steroid levels. The basis of uterine contractility is the interaction between actin and myosin in myometrial smooth muscle cells. This is driven by calcium through Ca 2+–calmodulin-dependent myosin light chain kinase (MLCK) activity. Moreover, calcium sensitisation occurs via activation of Rho kinase, a calcium-independent pathway that promotes contractility by inhibiting myosin phosphatase and probably by phosphorylating myosin on the same site as MLCK. Uterine activity can be modulated by many G-protein coupled receptors (GPCRs). For example, receptors coupled to Gα q (oxytocin-, prostanoid FP and TP, endothelin-receptors) stimulate contractility by activating the phospholipase C/Ca 2+ pathway; receptors coupled to Gα s (β 2-adrenoceptors, prostanoid EP2 and IP, some 5-hydroxytryptamine receptors e.g. 5-HT 7) relax the uterus by increasing myometrial cyclic AMP levels; and receptors coupled to Gα i (α 2-adrenoceptors, muscarinic, 5-HT 1) potentiate contractility, probably by inhibiting cAMP production. Because of its relative abundance in pregnant uterine tissue, the oxytocin receptor is an obvious target for tocolytic therapy. Oxytocin antagonists have been introduced into clinical practice for the management of preterm labour and offer the advantage of uterine selectivity and fewer side effects than conventional beta-agonist therapy.

Reproductive endocrine patterns in captive female and male red wolves (Canis rufus) assessed by fecal and serum hormone analysis

AbstractReproductive steroid profiles in female (n=13) and male (n=5) red wolves (Canis rufus) were characterized in fecal samples collected during the breeding season (December—May) and over a 1 year period, respectively. Blood samples from females (n=12) also were collected during the periovulatory period for luteinizing hormone (LH) and steroid analysis. High performance liquid chromatography (HPLC) of fecal extracts determined that estradiol and estrone constituted the major and minor forms, respectively, of fecal estrogen metabolites. Although native progesterone was present, pregnane metabolites predominated as the major forms of fecal progestins. HPLC analysis of fecal extracts from males revealed no native testosterone, but rather the predominance of more polar androgen metabolites. Based on hormone profiles and/or pup production, females were classified as pregnant (n=3), ovulatory‐nonpregnant (n=9), or acyclic (n=3). Longitudinal monitoring of females indicated no pregnancy‐specific differences in concentrations of either fecal progestagen or estrogen metabolites compared to ovulatory‐nonpregnant individuals; however, baseline progestagen concentrations were consistently elevated in acyclic females. There was good correspondence between serum and fecal steroid concentration during the periovulatory period. A rise in serum estrogens preceded the ovulatory LH surge which was then followed by a significant progesterone rise during the luteal phase. In males, changes in fecal androgen metabolite concentrations coincided with photoperiod fluctuations, increasing in late autumn and reaching peak concentrations during mid‐ to late winter just before the start of the breeding season. Collectively, these results serve as a database of ovarian and testicular endocrine events in this species, which can be utilized in population management and application of assisted reproductive technologies. Zoo Biol 21:321–335, 2002. © 2002 Wiley‐Liss, Inc.

Oestrogens alone or with amniotomy for cervical ripening or induction of labour.

Studies in sheep showed that there is a pre-labour rise in oestrogen and a decrease in progesterone, both of these changes stimulate prostaglandin production and may help initiate labour. Though oestrogen has been suggested as an effective cervical ripening or induction agent, research in humans have failed to demonstrate a similar physiological mechanism. The use of oestrogen as an induction agent is not currently common practice, as such this systematic review should be regarded as an historical review. This is one of a series of reviews of methods of cervical ripening and labour induction using a standardised methodology. To determine, from the best available evidence, the effectiveness and safety of oestrogens alone or with amniotomy for third trimester cervical ripening and induction of labour in comparison with other methods of induction of labour. The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and bibliographies of relevant papers. Last searched: April 2001. (1) randomised controlled trials comparing oestrogens alone used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods; (2) random allocation to the treatment or control group; (3) adequate allocation concealment; (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaningful outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusions. A generic strategy has been developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. The initial data extraction was done centrally. When comparing oestrogen with placebo there was no difference between the rate of caesarean section (7.1% versus 10.3%, relative risk (RR) 0.70, 95% confidence interval (CI) 0.30,1.62). There were no differences between rates of uterine hyperstimulation with or without fetal heart rate changes or instrumental vaginal delivery. None of the studies reported the rates of either vaginal delivery not achieved in 24 hours, or cervix unfavourable/unchanged after 12-24 hours. There were insufficient data to make any meaningful conclusions when comparing oestrogen with vaginal PGE2, intracervical PGE2, oxytocin alone or extra amniotic PGF2a, as to whether oestrogen is effective in inducing labour. There were insufficient data to draw any conclusions regarding the efficacy of oestrogen as an induction agent.

Developmental regulation of vascular endothelial growth/permeability factor messenger ribonucleic acid levels in and vascularization of the villous placenta during baboon pregnancy.

Vascular endothelial growth/permeability factor (VEG/PF) has an important role in angiogenesis; however, very little is known about the developmental regulation of VEG/PF and the vascular system within the placenta during human pregnancy. In the present study, therefore, a developmental approach was used in the baboon to determine the placental source of VEG/PF and its fms-like tyrosine kinase (flt-1) and kinase-insert domain containing (KDR/flk-1) receptors, and whether the rise in estrogen with advancing pregnancy was associated with a corresponding increase in placental VEG/PF expression and vascularization. VEG/PF messenger RNA (mRNA) levels were determined by competitive RT-PCR in villous cell fractions isolated by Percoll gradient centrifugation from placentas obtained on days 45 and 54 (very early), 60 (early), 100 (mid), and 165-170 (late) of baboon pregnancy (term = 184 days). Maternal peripheral serum estradiol increased from very low concentrations early in gestation (0.15-0.20 ng/ml) to an early surge of over 2.5 ng/ml on days 60-85, and peak levels of 4-6 ng/ml late in baboon pregnancy. VEG/PF mRNA was expressed in low level in the syncytiotrophoblast (<2,000 attomol/microgram total RNA), and values in this fraction did not change significantly with advancing gestation. VEG/PF mRNA expression was slightly greater in the inner villous core cell fraction; however, levels decreased (P < 0.05) between early and late gestation. Cytotrophoblasts were a major source of VEG/PF mRNA and levels increased (P < 0.01) from 3,631 +/- 844 attomol/microgram total RNA on day 45 to 25,807 +/- 5,873 attomol/microgram total RNA on day 170. VEG/PF protein expression determined by immunocytochemistry was abundant in cytotrophoblasts and lower in the syncytiotrophoblast and inner villous core cells. The flt-1 and KDR/flk-1 receptors were expressed in the vascular endothelial cells of the baboon villous placenta. The percentage of villous placenta occupied by blood vessels and the number of vessels/mm(2) villous tissue, determined by image analysis, progressively increased (P < 0.001; r = 0.97) from 3.4 +/- 0.2% and 447 +/- 29, respectively, on day 54 to 15.9 +/- 0.9% and 1,375 +/- 71, respectively, on day 170. In summary, the present study shows that villous cytotrophoblasts were a major source of VEG/PF mRNA and protein in the baboon villous placenta, and that cytotrophoblast VEG/PF mRNA levels and vascularization of the villous placenta closely paralleled the increase in estradiol concentrations of advancing pregnancy. These results are consistent with the concept that estrogen has an important role in establishing the new vascular system within the developing placenta during primate pregnancy and that VEG/PF mediates this process.

Stereotypes and Steroids: Using a Psychobiosocial Model to Understand Cognitive Sex Differences

To further our understanding of cognitive sex differences, we studied the relationship between menstrual phase (via serum estradiol and progesterone levels) and cognitive abilities and cognitive performance in a sample of medical students in eastern Turkey. As expected, we found no sex differences on the Cattell “Culture Fair Intelligence Test” (a figural reasoning test), with females scoring significantly higher on a Turkish version of the Finding A's Test (rapid word knowledge) and males scoring significantly higher on a paper-and-pencil mental rotation test. The women showed a slight enhancement on the Finding A's Test and a slight decrement in Cattell scores during the preovulatory phase of their cycle that (probably) coincided with a rise in estrogen. There were also small cycle-related enhancements in performance for these women on the mental rotation test that may reflect cyclical increases in estrogen and progesterone. Additional analyses showed an inverted U-shaped function in level of estradiol and the Cattell Test. Finally, for women who were tested on Day 10 of their menstrual cycle, there was a negative linear relationship between their Cattell scores and level of progesterone. Stereotypes about the cognitive abilities of males and females did not correspond to performance on the mental rotation or Finding A's Test, so the sex-typical results could not be attributed to either stereotype threat or stereotype activation. For practical purposes, hormone-related effects were generally small. Variations over the menstrual cycle do not provide evidence for a “smarter” sex, but they do further our understanding of steroidal action on human cognitive performance.

Why We Feel: The Science of Human Emotions

Why We Feel: The Science of Human Emotions

Environmental influence on reproductive health

A rise in industrialization and the consequent environmental pollution, an increase in the use of synthetic chemicals and repeated exposure to hazardous compounds at the workplace and at home adversely affects reproductive health. Biohazardous compounds, some of which act as endocrine disrupters, are being increasingly implicated in infertility, menstrual irregularities, spontaneous abortions, birth defects, endometriosis and breast cancer. In some cases, women are at a greater risk than men, especially with the rise in environmental estrogens. Only a fraction of these chemicals have been adequately examined for toxicity and for synergistic effects due to multiple exposures. There is a need for a greater awareness and vigilance of the effects of environmental pollution on reproductive health.

Steroid sulfatase inhibitor alters blood pressure and steroid profiles in hypertensive rats

Our hypothesis is that the steroid sulfatase gene ( Sts) may indirectly contribute to the modulation of blood pressure (BP) in rats with genetic hypertension. The steroid sulfatase enzyme (STS) catalyzes the conversion of estrone sulfate, dehydroepiandrosterone sulfate, cholesterol sulfate and glucocorticoid sulfates to their active nonconjugated forms. This causes the elevation of biologically active steroids, such as glucocorticoids, mineralcorticoids as well as testosterone, which may lead to increased BP. The main objective was to examine the effects of a steroid sulfatase inhibitor on blood pressure and steroid levels in rats with hypertensive genetic backgrounds. Three treatment groups, 5–15 weeks of age were used: controls, estrone and STS inhibitor (estrone-3- O-sulfamate), ( n=8 per group). BP was taken weekly by tail cuff, and serum testosterone (T), estrogens (E), and plasma corticosterone (C) levels were measured by radioimmunoassay. BP was significantly reduced by the STS inhibitor in the strains with genetically elevated BP. Also the inhibitor alone significantly reduced plasma corticosterone in all strains compared to estrone treatment with a concomitant as well as significant rise in estrogens and reduction in testosterone and body weight.

Circamensal Rhythmicity and Muscle Function: The Role of Reproductive Hormones in the Regulation of Strength

The human female menstrual cycle is characterised by fluctuations in reproductive and pituitary hormones which regulate the monthly release of an ovum for fertilisation. The circamensal changes in the hormonal milieu may influence exercise performance. The generation of maximal voluntary muscle strength, mediated by changes in the steroid hormones, has been the focus of recent research, particularly ergogenic effects of oestrogen. Peak force of the adductor pollicis, normalised for muscle size, has been reported mid-cycle in concert with the rise in oestrogen. The removal of an oestrogen and progesterone environment results in muscle weakness in humans and animals. These hormones decline concomitantly following natural ovarian failure (i.e., the menopause) and surgical extraction of the ovaries (i.e., bilateral oophorectomy). To overcome the problem of controlling for rapid cyclical changes in reproductive hormones across the menstrual cycle, and to isolate the effects of oestrogen when measuring strength, other models have been adopted. Treatment of in vitro fertilisation patients involves, in part, the down-regulation of gonadotropin releasing hormone receptors followed by up-regulation with exogenous pituitary hormones. This presents a very low and very high oestrogenic milieu while progesterone remains rel atively stable. Under these conditions, maximal strength of the first dorsal interosseus muscle has been unchanged. The rapid loss in strength observed post-menopause is preserved, and possibly restored, in women taking hormone replacement therapy. These findings are significant for the preservation of skeletal and muscular health of post-menopausal women. There is increasing evidence to support the role of reproductive hormones in the regulation of muscle strength. Since the link between the hormone milieu during the menstrual cycle and strength changes is weak, other models must be employed. Strength declines rapidly at the menopause, and offsetting muscle weakness in post-menopausal women has implications in reducing the risk of muscloskeletal injury. Female athletes who are prone to amenorrhoea constitute another target group. A hormone-deficient state may not be beneficial to performance, but may compromise muscle function.

How to cope with nosebleeds in pregnancy

Nosebleeds or epistaxes will happen to 60% of the normal population at sometime in their life (Doyle, 1986). It has been noted that there is an increased incidence in pregnancy although the actual increase has not been quantified. The actual mechanism of increased risk is thought to be related to the rise in oestrogen which produces nasal congestion from its effects on the parasympathetic nervous system and also the increase in systemic blood pressure seen in pregnancy.

Preimplantation hormonal differences between the conception and non-conception menstrual cycles of 32 normal women.

We compared daily urinary concentrations of oestrogen and progesterone metabolites in paired menstrual cycles (conception and non-conception) from 32 women. Volunteers with no known fertility problems were enrolled in the study at the time they began trying to become pregnant. They collected first-morning urine specimens and kept daily records of menstrual bleeding and sexual intercourse for 6 months or until they became clinically pregnant. Intercourse in non-conception cycles was close to the time of ovulation so that failure to conceive was caused by factors other than poorly timed intercourse. Compared with non-conception cycles, conception cycles had a steeper early luteal rise in progesterone and higher mid-luteal oestrogen and progesterone concentrations. These hormonal characteristics may be markers of better quality cycles, but because all these differences were in the luteal phase, we cannot rule out the possibility that the preimplantation embryo had stimulated early increases in steroid production. We propose an analysis strategy that could help support or refute the importance of preimplantation embryonic signalling, but our small sample size limits our own conclusions about this mechanism.

Alteration of ascending thoracic aorta compliance after treatment with menotropin

OBJECTIVE: Our purpose was to determine whether aortic size and compliance are altered by an exogenously induced rise in estrogen. STUDY DESIGN: Magnetic resonance imaging was used to determine the aortic cross-sectional area/aortic pressure relationship in nine premenopausal women before and after menotropin therapy. Simultaneous electrocardiograms, carotid pulse tracings, phonocardiograms, and brachial artery pressures were obtained before each magnetic resonance imaging acquisition. Ascending thoracic aorta cross-sectional area was obtained every 32 msec and aligned with brachial artery pressures extrapolated from the carotid pulse tracing, allowing construction of the ascending thoracic aorta cross-sectional area/aortic pressure relationships. Aortic cross-sectional area was normalized to body surface area, and the shifts in the position for the ascending thoracic aorta cross-sectional area/aortic pressure relationship were determined with use of analysis of covariance. RESULTS: Heart rate and aortic pressure were unchanged before and after menotropin treatment. Initial estradiol levels were <20 pg/ml. After menotropin treatment (7.4 ± 1.0 days) estradiol levels rose to 905 ± 371 pg/ml ( p < 0.0001). Ascending thoracic aorta cross-sectional area/body surface area was not significantly increased, adjusted y mean of 389 ± 7 mm 2/m 2 before and 403 ± 7 mm 2/m 2 after menotropin treatment ( p < 0.24). The slope of the ascending aorta cross-sectional area/aortic pressure relationship, an index of aortic compliance, increased from 1.4 ± 0.6 mm 2/m 2/mm Hg before to 1.7 ± 0.6 mm 2/m 2/mm Hg after menotropin treatment ( p < 0.001). CONCLUSION: In premenopausal women a short-term rise in estrogen induced by menotropin treatment is associated with an increase in aortic compliance. Aorta size is not significantly increased within this time frame. (Am J Obstet Gynecol 1997;176:1255-61.)

Secular trends in monitors of reproductive hazard.

There is concern that our reproductive systems are exposed to environmental hazards. A number of potential monitors of these hazards have been proposed (reported rates of cryptorchidism, testicular cancer, hypospadias, dizygotic twinning, sperm count, ectopic pregnancy and sex ratios). To discover whether these are monitoring the same hazards, secular movements in these measures are considered here. It is suggested that the secular movements of cryptorchidism and hypospadias are insufficiently reliable to give guidance on the movements of such hazards as cause them. With one possible exception, rates have not moved in parallel and so, in general, they are not monitoring the same hazards. The exception is dizygotic twinning rates and sperm counts which may have a lagged correlation. If this is true, it may be important and throw light on the hitherto unexplained movements of both. The hazards themselves are largely unidentified, but may be presumed to include: (i) the well-publicized rise in environmental oestrogens; (ii) an increasing number of women with suboptimal oestrogens (because of dieting and arduous exercise); and (iii) hormonal consequences of these two opposing trends, e.g. an increasing number of women with suboptimal androgens (possibly accounting for the increasing rates of cryptorchidism and testicular cancer).

Regulation of differentiation and keratin 10 expression by all-trans retinoic acid during the estrous cycle in the rat vaginal epithelium.

In rodents, the vaginal epithelium shows cyclic changes with an alternating pattern of keratinization under estrogen control and mucification under progesterone control. Retinoids are powerful regulators of cell differentiation, an excess of retinoids suppressing the keratinizing differentiation of keratinocytes. Here, we have examined the vaginal epithelium during the estrous cycle and compare the effects of retinoids on both types of hormonally induced differentiation, i.e. keratinization and mucification. All-trans retinoic acid was administered either by daily injections during the estrous cycle or by a single injection before the estrogen rise; these two protocols gave similar results. Retinoic acid suppressed estrogen-induced vaginal keratinization and cytokeratin K10 expression (a biochemical marker of terminal differentiation). Progesterone-induced mucification was not impaired; however, retinoic acid impeded mucous cell desquamation, suggesting an effect of retinoic acid on cell adhesiveness. Retinoic acid induced the appearance of apoptotic-like cells, as revealed by immunocytochemical staining of DNA fragmentation.

Hypertension and cardiovascular disease risk in women.

Hypertension and cardiovascular disease risk in women.