Effects Of Estradiol Treatment Research Articles

NLRC5 expression profile in the oviduct of laying hens and its changes following estradiol treatment in induced molting hens

The innate immune defense system is initiated by recognizing components of microorganisms by different families of receptors such as TLRs and the intracellular NLR family. Among the NLR family, NLRC5 recognizes pathogenic components of microorganisms. The current study aimed to determine the expression profile of NLRC5 in the mucosal tissue of the oviduct of laying hens and to examine the effects of oviduct regression and estradiol benzoate (EB) on its expression. In this study, we used two groups of laying and molting hens. The molting group was treated by receiving a single dose of sesame oil or estradiol benzoate through intramuscular injection. To examine the histological differences in the oviduct between laying, molting, and estradiol-injected groups, Tissue samples from all segments of the oviduct of all groups were fixed in formalin and stained with hematoxylin and eosin. To observe the profile of NLRC5 gene and the effects of estradiol treatment, RNA was obtained from the surface epithelium and lamina propria of the whole segments of the oviduct of normal laying hens, and mucosal tissue of magnum, isthmus, uterus, and the vagina of molting groups. Both mucosal surface epithelium and lamina propria expressed NLRC5. The expression of NLRC5 was higher in the molting than in the laying group, and it was lower in the EB group. These results suggested that NLRC5 may have a role in recognizing pathogens invading the oviduct of laying and molting hens, and its expression is changed in association with oviduct growth. Bangladesh J. Zool. 51(3): 345-359, 2023                                            

Oestrogen therapy for postpartum depression: efficacy and adverse effects. A double-blind, randomized, placebo-controlled pilot study

Background Postpartum depression (PPD) is detrimental to the mother and the family as a whole. Early initiation of appropriate treatment is important. The aim of this pilot study was to evaluate the efficacy and adverse effects of oestradiol treatment. Methods We performed a pilot double-blind, randomized, placebo-controlled study. Major depression was diagnosed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), and the severity of depression was evaluated using the Edinburgh Postnatal Depression Scale (EPDS). The duration of treatment with sublingual oestradiol hemihydrate (1–3 mg/day) was 12 weeks. Results The treatment group consisted of 16 mothers and the placebo group of 14 mothers. Thirteen mothers in the treatment group and ten in the placebo group recovered from depression during the treatment period as measured with the EPDS (<10). There was no evidence to suggest that oestradiol was more effective than placebo. More mothers in the treatment group than in the placebo group (eight vs. one) received gestagen treatment for irregular bleeding. Oestradiol did not disturb breastfeeding. The mean number of other adverse effects per mother was lower in the treatment group, and these were mostly somatic symptoms. Conclusion Our findings warrant further studies on oestrogen therapy for PPD with and without antidepressant and gestagen therapy, and on adverse effects (including effects on vaginal bleeding and breastfeeding).

A study on steroidogenic elaborations of stroma and their regulation in response to ovarian hormones in goats

Stromal tissue is an essential componenlt of the ovary not only for providing structural support but also for contributing to the early follicular growth with their bi-directional paracrine signaling. Estradiol is a major female hormone mainly secreted by the follicular cells in the ovary. To examine the relationship between 17β-estradiol and the factors involved in androgen production in stromal cells, ovarian stromal cells were cultured in the graded concentrations (50 and 100 ng/mL) of 17β-estradiol for varying time periods (24 and 48 h). The cells were processed for transmission electron microscopy to study the changes in steroidogenic functions of the cells. The effect of estradiol treatment was also evaluated on the quantity of androgen production and abundance of steroidogenic enzymes and proteins. The results indicated 17β-estradiol increased androgen production in ovarian stromal cells. In addition to enhanced androstenedione and testosterone production, estradiol stimulation was also based on the marked increase in abundance of mRNA transcript of steroidogenic enzymes [Star (Steroidogenic Acute Regulatory Protein), Cyp11a1, Cyp17a1, and hsd3b1 (3β-hydroxysteroid dehydrogenase)], as well as abundances of StAR and CYP11A1 protein. Thus, 17β-estradiol enhanced steroidogenesis in ovarian stromal cells. This study provided a basis for further exploration of regulation of steroidogenesis in ovarian stromal cells and the feedback mechanisms in association with estradiol.

Activation of the brain-pituitary-gonadotropic axis in the black porgy Acanthopagrus schlegelii during gonadal differentiation and testis development and effect of estradiol treatment

Previous studies revealed an estradiol (E2)-dependent peak in brain activity, including neurosteroidogenesis and neurogenesis in the black porgy during the gonadal differentiation period. The brain-pituitary-gonadotropic axis is a key regulator of reproduction and may also be involved in gonadal differentiation, but its activity and potential role in black porgy during the gonadal differentiation period is still unknown. The present study analyzed the expression of regulatory factors involved in the gonadotropic axis at the time of gonadal differentiation (90, 120, 150 days after hatching [dah]) and subsequent testicular development (180, 210, 300 dah). In agreement with previous studies, expression of brain aromatase cyp19a1b peaked at 120 dah, and this was followed by a gradual increase during testicular development. The expression of gonadotropin subunits increased slightly but not significantly during gonadal differentiation and then increased significantly at 300 dah. In contrast, the expression of brain gnrh1 and pituitary gnrh receptor 1 (gnrhr1) exhibited a pattern with two peaks, the first at 120 dah, during the period of gonadal differentiation, and the second peak during testicular development. Gonad fshr and lhcgr increased during gonadal differentiation period with highest transcript level in prespawning season during testicular development. This suggests that the early activation of brain gnrh1, pituitary gnrhr1 and gths, and gonad gthrs might be involved in the control of gonadal differentiation. E2 treatment increased brain cyp19a1b expression at each sampling time, in agreement with previous studies in black porgy and other teleosts. E2 also significantly stimulated the expression of pituitary gonadotropin subunits at all sampling times, indicating potential E2-mediated steroid feedback. In contrast, no significant effect of E2 was observed on gnrh1. Moreover, treatment of AI or E2 had no statistically significant effect on brain gnrh1 transcription levels during gonadal differentiation. This indicated that the early peak of gnrh1 expression during the gonadal differentiation period is E2-independent and therefore not directly related to the E2-dependent peak in brain neurosteroidogenesis and neurogenesis also occurring during this period in black porgy. Both E2-independent and E2-dependent mechanisms are thus involved in the peak expression of various genes in the brain of black porgy at the time of gonadal differentiation.

Action of adrenal and gonadal steroid hormones on kainic acid-evoked seizures in a rat model of epileptogenesis

ABSTRACTEpilepsy is one of most reported neurological disorders after migraine, stroke and Alzheimer's disease. Empiric clinical data reveal that seizures and epilepsy more likely affect men than women. The aim of present study was to investigate the effect of steroid adrenal and gonadal hormones on the intensity, dynamics and latency of kainic acid-evoked seizure and lethality in a rat model of epileptogenesis. After surgical adrenalectomy/gonadectomy, male rats were at random assorted in groups and treated from postoperative day 1 to day 5 with corticosterone (30 mg/kg), estradiol (0.03 mg/kg), progesterone (75 mg/kg), dihydroprogesterone (75 mg/kg) and dihydrotestosterone (0.75 mg/kg). Spontaneous recurrent seizures generated by kainic acid were assessed. The treatment with corticosterone eliminated the aggravation of kainic acid-evoked seizures produced by adrenalectomy/gonadectomy. The application of corticosterone decreased the seizure intensity by 31% and prevented seizure-associated animal death. The effect of estradiol treatment was quite opposite. Estradiol treatment exacerbated the somatic and behavioural aspects of kainic acid-evoked epilepsy-like syndrome. The hormone increased the intensity of kainic acid-evoked seizures by 31%, decreased the latency of clonic weak seizures by 49% and enhanced the associated lethality by 133%. The treatment with progesterone or dihydroprogesterone produced minor alterations in intensity and latency of kainic acid-evoked seizures in the operated male rats. The application of dihydrotestosterone significantly aggravated the kainic acid-evoked seizures. In summary, hormonal unbalance could play an important role for seizure susceptibility in epileptogenesis. Corticosterone has better anti-seizure activity than progesterone and testosterone has significant pro-convulsive activity.

Protective Role of Estrogen-induced miRNA-29 Expression in Carbon Tetrachloride-induced Mouse Liver Injury

Previous studies have indicated that female animals are more resistant to carbon tetrachloride (CCl(4))-induced liver fibrosis than male animals, and that estradiol (E(2)) treatment can inhibit CCl(4)-induced animal hepatic fibrosis. The underlying mechanism governing these phenomena, however, has not been fully elucidated. Here we reported the role of estrogen-induced miRNA-29 (miR-29) expression in CCl(4)-induced mouse liver injury. Hepatic miR-29 levels were differentially regulated in female and male mice during CCl(4) treatment. Specifically, the levels of miR-29a and miR-29b expression were significantly decreased in the livers of male, but not female, mice following 4 weeks of CCl(4) treatment. The down-regulation of miR-29a and miR-29b in male mouse livers correlated with the early development of liver fibrosis, as indicated by increased expressions of fibrotic markers in male mice relative to female mice. In addition, E(2) was maintained at a higher level in female mice than in male mice. In contrast to TGF-β1 that decreased miR-29a/b expression in murine hepatoma IAR20 cells and normal hepatocytes, E(2) enhanced the expression of miR-29a/b through suppression of the nuclear factor-κB (NF-κB) signal pathway, which negatively regulates miR-29 expression. Furthermore, both E(2) treatment and intravenous injection of the recombinant adenovirus expressing miR-29a/b markedly increased the miR-29a/b level and attenuated the expression of fibrotic markers in mouse livers during CCl(4) treatment, supporting the protective role of E(2)-induced miR-29 in CCl(4)-induced hepatic injury. In conclusion, our results collectively demonstrate that estrogen can inhibit CCl(4)-induced hepatic injury through the induction of hepatic miR-29.

Why the bulge?: the differential expression of elastic fibril components in leiomyoma (LEIO) and myometrium (MYO) and effects of estradiol treatment

Why the bulge?: the differential expression of elastic fibril components in leiomyoma (LEIO) and myometrium (MYO) and effects of estradiol treatment

Ovarian hormone‐induced reorganization of oxytocin‐labeled dendrites and synapses lateral to the hypothalamic ventromedial nucleus in female rats

Central oxytocin (OT) modulates many social behaviors, including female rat sexual receptivity, quantified as the copulatory stance known as lordosis. The expression of the lordosis response is modulated by OT action in the ventromedial nucleus of the hypothalamus (VMH), as demonstrated by behavioral pharmacology experiments. However, the subcellular localization of OT in this brain region has been unclear. We tested the hypothesis that ovarian hormones reorganize OT-labeled pre- or postsynaptic elements in the fiber complex lateral to the VMH by using immunoelectron microscopy. OT immunolabeling occurred in axonal boutons identified by the presence of small, clear synaptic vesicles and double labeling with the presynaptic markers synaptophysin and vesicular glutamate transporter 2. OT immunoreactivity also was observed in dendritic profiles, verified with double labeling for the dendrite-specific marker microtubule-associated protein 2. Ovarian hormones did not alter the density of axonal boutons; however, estradiol treatment reduced the density of dendritic profiles by 34%. This effect was reversed when progesterone was given subsequent to estradiol. The effect of estradiol treatment was specific to dendrites that lacked OT immunostaining; the density of OT-labeled dendritic profiles remained constant during estradiol treatment. With the estradiol-induced exit of non-OT-labeled dendritic profiles, the remaining OT-labeled dendritic profiles experienced an increase in their number of synaptic contacts. Thus, hormone treatments that mimic the 4-day rat estrous cycle provoke a chemically coded reorganization of dendrite innervation in the fiber plexus lateral to the VMH that may underlie the hormone-specific effect of OT on reproductive behavior.

Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype

Background:We aimed to clarify the incidence and the clinicopathological value of non-muscle myoglobin (Mb) in a large cohort of non-invasive and invasive breast cancer cases.Methods:Matched pairs of breast tissues from 10 patients plus 17 breast cell lines were screened by quantitative PCR for Mb mRNA. In addition, 917 invasive and 155 non-invasive breast cancer cases were analysed by immunohistochemistry for Mb expression and correlated to clinicopathological parameters and basal molecular characteristics including oestrogen receptor-α (ERα)/progesteron receptor (PR)/HER2, fatty acid synthase (FASN), hypoxia-inducible factor-1α (HIF-1α), HIF-2α, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX). The spatial relationship of Mb and ERα or FASN was followed up by double immunofluorescence. Finally, the effects of estradiol treatment and FASN inhibition on Mb expression in breast cancer cells were analysed.Results:Myoglobin mRNA was found in a subset of breast cancer cell lines; in microdissected tumours Mb transcript was markedly upregulated. In all, 71% of tumours displayed Mb protein expression in significant correlation with a positive hormone receptor status and better prognosis. In silico data mining confirmed higher Mb levels in luminal-type breast cancer. Myoglobin was also correlated to FASN, HIF-2α and CAIX, but not to HIF-1α or GLUT1, suggesting hypoxia to participate in its regulation. Double immunofluorescence showed a cellular co-expression of ERα or FASN and Mb. In addition, Mb levels were modulated on estradiol treatment and FASN inhibition in a cell model.Conclusion:We conclude that in breast cancer, Mb is co-expressed with ERα and co-regulated by oestrogen signalling and can be considered a hallmark of luminal breast cancer phenotype. This and its possible new role in fatty acid metabolism may have fundamental implications for our understanding of Mb in solid tumours.

Steroid hormone receptors ERα and PR characterised by immunohistochemistry in the mare adrenal gland

BackgroundSex steroid hormone receptors have been identified in the adrenal gland of rat, sheep and rhesus monkey, indicating a direct effect of sex steroids on adrenal gland function.MethodsIn the present study, immunohistochemistry using two different mouse monoclonal antibodies was employed to determine the presence of oestrogen receptor alpha (ERalpha) and progesterone receptor (PR) in the mare adrenal gland. Adrenal glands from intact (n = 5) and ovariectomised (OVX) (n = 5) mares, as well as uterine tissue (n = 9), were collected after euthanasia. Three of the OVX mares were treated with a single intramuscular injection of oestradiol benzoate (2.5 mg) 18 – 22 hours prior to euthanasia and tissue collection (OVX+Oe). Uterine tissue was used as a positive control and showed positive staining for both ERalpha and PR.ResultsERalpha staining was detected in the adrenal zona glomerulosa, fasciculata and reticularis of all mare groups. Ovariectomy increased cortical ERalpha staining intensity. In OVX mares and one intact mare, positive ERalpha staining was also detected in adrenal medullary cells. PR staining of weak intensity was present in a low proportion of cells in the zona fasciculata and reticularis of all mare groups. Weak PR staining was also found in a high proportion of adrenal medullary cells. In contrast to staining in the adrenal cortex, which was always located within the cell nuclei, medullary staining for both ERalpha and PR was observed only in the cell cytoplasm.ConclusionThe present results show the presence of ERalpha in the adrenal cortex, indicating oestradiol may have a direct effect on mare adrenal function. However, further studies are needed to confirm the presence of PR as staining in the present study was only weak and/or minor. Also, any possible effect of oestradiol treatment on the levels of steroid receptors cannot be determined by the present study, as treatment time was of a too short duration.

Estrogen receptor alpha and beta specific agonists regulate expression of synaptic proteins in rat hippocampus

Changes in hippocampal CA1 dendritic spine density and synaptic number across the estrous cycle in female rats correlate with increased hippocampal-dependent cognitive performance in a manner that is dependent on estrogen receptors (ERs). Two isoforms of the estrogen receptor, α and β are present in the rat hippocampus and distinct effects on cognitive behavior have been described for each receptor. The present study generated a profile of synaptic proteins altered by administration of estradiol benzoate, the ERα selective agonist PPT (1,3,5-tris (4-hydroxyphenyl)-4-propyl-1H-pyrazole) and the ERβ selective agonist DPN (2,3-bis (4-hydroxyphenyl) propionitrile) alone and in combination in comparison to vehicle in the CA1 region of the dorsal hippocampus. In the stratum radiatum, estradiol, DPN, and PPT increased PSD-95 and AMPA-type glutamate receptor subunit GluR1. Only DPN administration regulated expression of AMPA receptor subunits GluR2 and GluR3, increasing and decreasing levels respectively. DPN also increased GluR2 expression in the other lamina of the CA1. These results support previous reports that estradiol and isoform specific agonists differentially activate ERα and ERβ to regulate protein expression. The distinct effects of DPN and PPT administration on synaptic proteins suggest that the desired therapeutic outcome of estrogen may be accomplished by using specific estrogen receptor agonists. Moreover, the effects of estradiol treatment on PSD-95 expression are consistent with a growing body of evidence that this postsynaptic protein is a key marker of estrogen action related to spine synapse formation.

Low doses of estradiol partly inhibit release of GH in sheep without affecting basal levels

Estradiol increases basal growth hormone (GH) concentrations in sheep and cattle. This study sought to determine the effects of estradiol on GH-releasing hormone (GRH)-stimulated GH release in sheep. Growth hormone secretory characteristics, the GH response to GRH, and steady-state GH mRNA concentrations were determined in castrated male lambs treated with 2 different doses of estradiol 17-β for a 28-d experimental period. Although no differences between treatments in mean GH, basal GH, or GH pulse number were observed after 28 d of estradiol treatment, GH pulse amplitude was greater ( P < 0.05) in the 2.00-cm implant-treated animals than in the control and 0.75-cm implant group. The effect of estradiol treatment on GRH-stimulated GH release revealed differences between the control and estradiol-treated animals ( P < 0.05). The 15-min GH responses to 0.075 μg/kg hGRH in the control, 0.75-cm, and 2.00-cm implant groups, respectively, were 76 ± 10, 22.6 ± 2.1, and 43.6 ± 15.0 ng/mL. Growth hormone mRNA content was determined for pituitary glands from the different treatment groups, and no differences in steady-state GH mRNA levels were observed. There were no differences in the mean plasma concentrations of IGF-I, cortisol, T 3, or T 4 from weekly samples. Growth hormone release from cultured ovine pituitary cells from control sheep was not affected by estradiol after 72 h or in a subsequent 3-h incubation with estradiol combined with GRH. These data suggest that estradiol has differing actions on basal and GRH-stimulated GH concentrations in plasma, but the increase in pulse amplitude does not represent an increased pituitary sensitivity to GRH.

Effects of Estradiol Treatment and/or Ovariectomy on Spontaneous Hemorrhagic Lesions in the Pancreatic Islets of Sprague-Dawley Rats

The present study was conducted to investigate the effect of estradiol treatment and/or ovariectomy (OVX) on non-neoplastic lesions in the pancreatic islets of Sprague-Dawley rats. Males were divided into non-treatment (naïve) and beta-estradiol 3-benzoate (EB) treatment groups and females into naïve, sham-operation, OVX, and OVX plus EB treatment groups. EB was subcutaneously administered once a week from seven to twenty-six weeks of age. The animals were euthanized at twelve, eighteen, and twenty-six weeks of age, and the serum estradiol concentrations were measured in conjunction with the pancreatic islet histopathology. The histological stages of pancreatic findings were classified into three groups, hemorrhagic, fibrotic, and inflammatory lesions, and the incidence of each type of lesion was enumerated. In males, both the total and individual incidence of pancreatic lesions increased age dependently in the naïve group. EB treatment significantly decreased the total incidence at twenty-six weeks. This alteration consisted of fibrotic and inflammatory lesions, but not hemorrhagic lesions. Additionally, the incidence of hemorrhagic lesions was at the same level between male naïve and male EB groups at twelve weeks, despite a markedly higher concentration of serum estradiol in the EB group. In females, a similar tendency was seen, and the total incidence was generally low in the naïve group, whereas it was increased by OVX. OVX plus EB treatment tended to decrease the incidence accompanied by a marked increase in estradiol concentrations. In conclusion, estrogen was shown to inhibit the development of pancreatic islet lesions toward inflammation and fibrosis but did not inhibit the occurrence of hemorrhagic lesions.

Estradiol treatment and its interaction with the cholinergic system: Effects on cognitive function in healthy young women

The steroid hormone estradiol has been shown to modulate cognitive function in both animals and humans, and although the exact mechanisms associated with these effects are unknown, interactions with the cholinergic system have been proposed. We examined the neurocognitive effects of short-term estradiol treatment and its interaction with the cholinergic system using the muscarinic receptor antagonist scopolamine in healthy young women. Thirty-four participants (Mean age ± SD = 22.4 ± 4.4) completed baseline cognitive assessment and then received either 100 μg/day transdermal estradiol or transdermal placebo for 31 days. On days 28 and 31 of treatment, further cognitive assessment was performed pre- and 90 min post-scopolamine (0.4 mg) or placebo (saline) injection, under a randomized double-blind placebo-controlled design. Short-term estradiol treatment significantly enhanced spatial working memory with a trend for improvement in long-term verbal learning and memory. Overall, estradiol treatment did not protect against or attenuate the scopolamine-induced impairments in the cognitive domains assessed. Findings suggest that estrogen has minimal effects on cholinergic-mediated cognitive processes following short-term treatment. Effects of estradiol treatment may be dependent on age, dose of estradiol, integrity of cholinergic innervation and baseline endogenous estrogen levels, which may in part explain the inconsistent findings in the literature.

Chronic Estradiol Treatment Improves Brain Homeostasis during Aging in Female Rats

Aging is associated with a reduction in metabolic function, insulin resistance, increased incidence of neurodegenerative diseases, and memory or cognitive dysfunction. In aging females, loss of gonadal function determines the beginning of the period of reduced metabolic function. Estrogens have neuroprotective effects, but the mechanisms by which they exert these effects remain unclear. The effects of estradiol treatment on the activation of the insulin receptor substrate (IRS)-1 signaling pathway, the interactions between estrogen receptor (ER)-alpha and IRS-1 and the p85alpha subunit of phosphatidylinositol-3 kinase, together with the possible effects of estradiol treatment on glucose transporter-3 and -4 levels, were investigated in female rats. The level of expression of each glucose transporter was greater in control and estradiol-treated groups than in the ovariectomized group. Interactions of ERalpha46-IRS-1, ERalpha46-p85alpha, and p85alpha-IRS-1, as well as IRS-1 phosphorylation, appeared to increase with estradiol treatment. The results indicate that estradiol treatment improves some aspects of neuronal homeostasis that are affected by aging; this may indicate that estradiol has neuroprotective effects in female rats. Additional animal studies are required to clarify the neuroprotective role of estradiol in relation to other important molecules involved in the IRS-1-phosphatidylinositol-3 kinase signaling pathway.

Estrogen activates rapid signaling in the brain: Role of estrogen receptor α and estrogen receptor β in neurons and glia

The aging process is known to coincide with a decline in circulating sex hormone levels in both men and women. Due to an increase in the average lifespan, a growing number of post-menopausal women are now receiving hormone therapy for extended periods of time. Recent findings of the Women’s Health Initiative, however, have called into question the benefits of long-term hormone therapy for treating symptoms of menopause. The results of this study are still being evaluated, but it is clear that a better understanding of the molecular effects of estradiol is needed in order to develop new estrogenic compounds that activate specific mechanisms but lack adverse side effects. Traditionally, the effects of estradiol treatment have been ascribed to changes in gene expression, namely transcription at estrogen response elements. This review focuses on emerging information that estradiol can also activate a repertoire of membrane-initiated signaling pathways and that these rapid signaling events lead to functional changes at the cellular level. The various types of cells in the brain can respond differently to estradiol treatment based on the signaling properties of the cell, as well as which receptor, estrogen receptor α and/or estrogen receptor β, is expressed. Taken together, these findings suggest that the estradiol-induced activation of membrane-initiated signaling pathways occurs in a cell-type specific manner and can differentially influence how the cells respond to various insults.

Analysis of genes related to expression of aromatase and estradiol-regulated genes during sex differentiation in Xenopus embryos

We analyzed the genes that exhibit transcriptional changes during sex differentiation in Xenopus, using fluorescent differential display (FDD). Search was then undertaken for sequences that were homologous to the differentially displayed DNA. In this report, trans-acting factors of activating transcription factor 4 (ATF 4) and heat shock proteins were selected, on the basis of homology, from candidate genes thought to be involved in the expression cascade of aromatase and estrogen receptor genes. The stage and tissue specificities and the effect of estradiol treatment on the expression of these genes were then examined using real-time quantitative polymerase chain reaction (RQ-RT-PCR). The expression of ATF 4, a member of the ATF/cAMP-responsive element-binding protein (CREB) family of genes, peaked in the gonads at stage 50 of development. Interestingly, expression of the genes encoding the heat shock cognate protein70. II (Hsc70. II) and the heat shock protein 70 (Hsp70) binding protein was strongly activated at stages 50 and 48 of development, respectively. The three genes revealed a higher transcription activity in the gonads than in other tissues. Although the expression of all of the genes encoding ATF 4, aromatase, Hsc70. II, and Hsp70 binding protein was activated in vitro by estrogen treatment, that of Hsc70. II and Hsp70 binding protein was found to be transient.

Effects of onapristone on postmenopausal endometrium

The progesterone antagonist mifepristone (RU486, Exelgyn) has been shown to exert a paradoxical agonist effect on postmenopausal endometrium. We conducted a study to investigate the effects of the ‘pure’ antiprogestin onapristone (ZK 98 299, Schering AG) on postmenopausal endometrium. Seventeen postmenopausal subjects (45–62 years), took 2 mg of oestradiol and either placebo, 1 mg onapristone or 10 mg of onapristone, daily for 56 days. An endometrial biopsy was performed during the final week of treatment and assessed for histology and immunohistochemistry for oestrogen receptors (ER), progesterone (PR), androgen receptors (AR) and the cell proliferation marker Ki 67. FSH fell in all 14 subjects who completed the study, consistent with the effect of oestradiol treatment. There was a dose-dependent additive effect of onapristone on suppression of gonadotrophins. All endometrial biopsies showed proliferative endometrium. A similar pattern and intensity of immunostaining of ER, PR and Ki 67 was observed in all groups, with positive immunoreactivity in both glands and stroma. AR immunostaining was observed in both glands and stroma from all subjects, but there was an increase in intensity of immunostaining within the glandular epithelium of women receiving 10 mg onapristone. The antiprogestin onapristone, in contrast to mifepristone, is not agonistic on postmenopausal endometrium and does not exert obvious antiproliferative effects. It does however cause a dose dependent suppression of FSH and LH release.

Effect of oestradiol treatment on mast cell populations and microflora in the vaginal cul-de-sac of seasonally anoestrous brushtail possums (Trichosurus vulpecula).

Mast cell populations in the vaginal cul-de-sac of female brushtail possums do not appear to be related to microbial invasion but changes in their density occur at oestrus, indicating a hormonal influence. The present study examined the effect of treatment with oestradiol on microflora and on mast cell numbers and their spatial location in cul-de-sac tissue of seasonally anoestrous brushtail possums. Tissue was collected from seasonally anoestrous brushtail possums (n = 6 per group) that were either untreated (anoestrous group) or were subjected to 6 days of treatment with oestradiol (oestradiol group) administered via subcutaneous implants or with the oil vehicle alone (control group). Tissue was collected aseptically for microbiological procedures and the fractionator and optical disector were used to quantify mast cell populations. Microflora populations were low (< 4.0 x 10(4) organisms g(-1)) and numbers of mast cells were similar in all groups. Mast cell density was greatest in epithelial and connective tissues from seasonally anoestrous and control animals and lowest in oestradiol-treated possums, in which there was a significant increase in cul-de-sac mass and volume. There is an inverse relationship between circulating oestrogen concentrations and mast cell density in possum cul-de-sac tissue, which is probably the result of an increase in tissue volume.

Effect of oestradiol treatment on mast cell populations and microflora in the vaginal cul-de-sac of seasonally anoestrous brushtail possums (Trichosurus vulpecula)

Mast cell populations in the vaginal cul-de-sac of female brushtail possums do not appear to be related to microbial invasion but changes in their density occur at oestrus, indicating a hormonal influence. The present study examined the effect of treatment with oestradiol on microflora and on mast cell numbers and their spatial location in cul-de-sac tissue of seasonally anoestrous brushtail possums. Tissue was collected from seasonally anoestrous brushtail possums (n = 6 per group) that were either untreated (anoestrous group) or were subjected to 6 days of treatment with oestradiol (oestradiol group) administered via subcutaneous implants or with the oil vehicle alone (control group). Tissue was collected aseptically for microbiological procedures and the fractionator and optical disector were used to quantify mast cell populations. Microflora populations were low (< 4.0 x 10(4) organisms g(-1)) and numbers of mast cells were similar in all groups. Mast cell density was greatest in epithelial and connective tissues from seasonally anoestrous and control animals and lowest in oestradiol-treated possums, in which there was a significant increase in cul-de-sac mass and volume. There is an inverse relationship between circulating oestrogen concentrations and mast cell density in possum cul-de-sac tissue, which is probably the result of an increase in tissue volume.