Tissue Progesterone Research Articles

Protein expression of estrogen, progesterone, and human epidermal growth factor receptors in young Iraqi women with breast cancer

Breast cancer is currently evaluated by the presence of hormonal receptors in the tumor tissue, which are among the most important prognostic and predictive markers used at present. The current study was conducted in Thi-Qar Governorate (Iraq) on women aged 20-40 years who have breast cancer (BC), highlighting­ the spread of this disease among young groups. The expression of estrogen (ER), progesterone (PR), and human epidermal growth factor (Her2/neu) receptors in breast tissues using immunohistochemical analysis was estimated. Breast tissue samples were collected from patients undergoing breast surgery and biopsy. Formalin-fixed paraffin-embedded samples were divided into BC (80), and control (20) groups. The study found that protein expression of both ER and PR was positive in 87.5% and negative in 12.5%, Her2/neu positive in 60% and negative in 40% of BC samples. The subtypes identified were luminal A (58.75%), luminal B (31.25%), HER2-positive (6.25%), and triple-negative (3.75%) BC. The high percentage of luminal A molecular subtype of BC is considered a good prognosis and treatable by anti-hormonal therapy. Keywords: breast cancer, estrogen, human epidermal growth factor, immunohistochemistry, progesterone, receptors

389 Impact of a Controlled Internal Drug Release device on circulating and local concentrations of progesterone

Abstract Controlled Internal Drug Release (CIDR) devices have become an important component of reproductive management programs in many beef herds. When a CIDR is inserted into a cow, circulating concentrations of progesterone mimic a functional corpus luteum. Some data, however, suggest that concentration of progesterone following insertion of a CIDR might have negative consequences on fertility in Bos indicus animals. Therefore, the objective of this study was to determine the impact of a CIDR device on circulating and uterine tissue concentrations of progesterone. A blood sample and a uterine biopsy were collected from non-suckled postpartum cycling Brahman cows (n = 10; Cycling) during the midluteal stage. A blood sample and a uterine biopsy were also collected from non-suckled postpartum cycling Brahman cows (n = 9; CIDR) after a CIDR had been in place for 5 d. To collect uterine biopsies from CIDR cows, the uterine biopsy tool was placed inside a plastic covering, both were passed into the cervix of the cow before the tool was extended through the covering and into the uterus. After the biopsy was collected, the tool was carefully removed to prevent sample contamination. Blood samples were centrifuged, and serum was collected to determine concentrations of progesterone. Uterine biopsies were snap frozen until extraction. Biopsies were weighted, thawed, and homogenized in assay buffer. Samples were then extracted with methyl tert-butyl ether and resuspended in assay buffer. Serum concentrations are reported as ng/mL and uterine concentrations are reported as ng/g. Statistical analysis was performed using the GLM procedure in SAS with treatment (CIDR vs Cycling), tissue type (uterine vs serum) and their interaction included in the model. There was a significant effect of treatment (P = 0.0062), tissue (P = 0.0063) and a treatment by tissue interaction (P = 0.0068). Animals with a CIDR had greater concentrations of progesterone than Cycling animals (274.77 vs 4.37 ng, respectively). Uterine samples had greater concentrations of progesterone than serum samples (274.40 vs 4.74 ng, respectively). These increased concentrations of progesterone were mainly from CIDR uterine samples (543.24 ng/g) which had greater (P < 0.001) concentrations of progesterone compared with all other samples, which did not differ from each other (P > 0.98; CIDR Serum 6.29 ng/mL, Cycling Serum 3.2 ng/mL, and Cycling Uterus 5.54 ng/g). In summary, CIDRs increased circulating concentrations of progesterone sufficient to keep animals from exhibiting estrus, and were not different from cows in the midluteal stage of their cycle. Local concentrations in uterine tissue; however, were significantly greater when a CIDR was in place compared with uterine tissue collected during the midluteal phase. The implications of these significantly greater concentrations of progesterone in uterine tissue warrant further investigation.

The role of progesterone and estrogen receptors in treatment choice after endometriosis surgery: A cross-sectional study.

The lack of improvement in some endometriotic people's pain after surgery even while using hormone treatment may suggest an inappropriate response to routine hormonal therapies. This study aimed to determine a cut-off point for selecting the most appropriate treatment based on the hormone receptors of endometriotic lesions. In this cross-sectional study, by reviewing the medical records of participants and testing their archive samples and phone interviews (if needed), 86 symptomatic women after endometriosis surgery who were operated into governmental hospitals, Shahid Faghihi and Hazrate Zeinab Shiraz Iran were enrolled between March 2017 and March 2019. Women were divided into 2 groups: responsiveness (n = 73 for dysmenorrhea, n = 60 for dyspareunia) to medical treatment and surgery, and unresponsiveness (n = 13, n = 7). We examined the pathological slides of 86 women to determine the amount of hormone receptors and the relationship between the type of medical treatment and the level of hormone receptors on pain relief within 1 yr after surgery. Based on the receiver operating characteristic curve, dysmenorrhea in the presence of tissue estrogen receptors 60% (p = 0.1065), and dyspareunia in the presence of tissue progesterone receptors 80% (p = 0.0001) responded well to medical treatment after surgery. In the presence of endometrioma-dysmenorrhea showed the best response to oral contraceptive pills (69.4%), while in deep infiltrative endometriosis-dyspareunia showed the best response to progesterone treatment (75%). Prescribing an appropriate hormone therapy based on a specific immunohistochemistry staining pattern can improve the life quality of postoperative endometriosis individuals.

Mechanisms of adverse mammary effect induced by olanzapine and therapeutic interventions in rat model.

BackgroundOlanzapine antagonizes dopamine receptors and is prescribed to treat multiple psychiatric conditions. The main side effect of concern for olanzapine is weight gain and metabolic syndrome. Olanzapine induces hyperprolactinemia, however its effect on the mammary gland is poorly documented. MethodsRats received olanzapine by gavage or in drinking water at 1, 3, and 6 mg/kg/day for 5–40 days or 100 days, with and without coadministration of bromocriptine or aripiprazole and using once daily or continuous administration strategies. Histomorphology of the mammary gland, concentrations of prolactin, estradiol, progesterone, and olanzapine in serum, mammary gland and adipose tissue, and mRNA and protein expressions of prolactin receptors were analyzed. ResultsIn adult and prepubescent female rats and male rats, olanzapine induced significant development of mammary glands in dose- and time-dependent manners, with histopathological hyperplasia of mammary ducts and alveoli with lumen dilation and secretion, marked increase of mammary prolactin receptor expression, a marker of breast tissue, and with mild increase of circulating prolactin. This side effect can be reversed after medication withdrawal, but long-term olanzapine treatment for 100 days implicated tumorigenic potentials indicated by usual ductal epithelial hyperplasia. Olanzapine induced mammary development was prevented with the coaddition of the dopamine agonist bromocriptine or partial agonist aripiprazole, or by continuous administration of medication instead of a once daily regimen. ConclusionsThese results shed light on the previously overlooked effect of olanzapine on mammary development and present experimental evidence to support current clinical management strategies of antipsychotic induced side effects in the breast.

Ganaxolone: First FDA-Approved Medicine for the Treatment of Seizures Associated with Cyclin-dependent Kinase-like 5 Deficiency Disorder.

The neurosteroids progesterone and allopregnanolone control numerous neuroprotective functions in neural tissues, including inhibition of epileptic seizures and cell death. Ganaxolone (3α-hydroxy-3β-methyl-5α-pregnan-20-one) (GNX) is the 3β-methylated synthetic analog of allopregnanolone and an allosteric GABAA positive modulator. Ganaxolone reduces the frequency of CDD-associated seizures.

Reasons and Mechanisms of Development of Mastopathy (Review of Literature)

This review article examines the relationship between various etiological factors in the development of mastopathy. Multiple exogenous and endogenous risk factors disrupt the normal ratio of sex hormones, causing hyperestrogenism and hyperproliferation of the epithelium in breast tissue, which leads to the development of mastopathy. In the presence of polymorphism of coding genes (ESR1 and PRG), mastopathy also increases the risk of developing breast cancer. Disturbances in the ESR1 receptor gene (Estrogen Receptor 1) lead to changes in the sensitivity of receptors to hormones and even to its loss. According to the literature, polymorphism in the intronic region of the ESR1 gene is associated with the risk of fibrocystic mastopathy. The presence of polymorphism of the PRG (Progesterone Receptor Genes) gene may cause the occurrence of defective forms of PR (Progesterone Receptor) with disruption of the ligand- and hormone-binding zones, which is confirmed by the effects of progesterone in tissues. Thus, progesterone deficiency makes possible excessive proliferation of not only epithelial cells, but also the connective tissue component of the mammary gland. In this case, the expression of the progesterone receptor gene is regulated by the level of estrogen. The association of various combinations of predisposition genes indicates the presence of a specific combination of genotypes for each clinical and pathogenetic variant. In proliferative forms of mastopathy, foci with an excess content of estrogen receptors in the epithelium and high activity of cell proliferation and apoptosis are formed in the breast tissue; there is an increase in the content of alpha-estrogen receptors, a change in the relative content of alpha- and beta-estrogen receptors, A- and B-progesterone receptors; the sensitivity of the epithelium to estradiol increases; a complex of cyclin-dependent kinases, alpha-transforming and epidermal growth factors is activated; the proliferative activity of the epithelium increases; apoptosis processes are disrupted; vascularization of the parenchyma increases. All these pathological mechanisms that increase the risk of breast cancer have not yet been sufficiently studied both at the experimental and clinical level. In the treatment of mastopathy, diet therapy, psychological correction, hormonal drugs, non-hormonal drugs, such as vitamins, minerals, hepatoprotectors, diuretics, enzyme drugs, immunocorrectors, adaptogens, non-steroidal anti-inflammatory drugs, herbal remedies are used. The general disadvantages of most of the remedies used today are attempts to eliminate the causes of mastopathy rather than conducting pathogenetic treatment.

Dietary progesterone contributes to intra-tissue levels of progesterone in male mice.

Progesterone serum levels have been identified as a potential predictor for treatment effect in men with advanced prostate cancer, which is an androgen-driven disease. Although progesterone is the most abundant sex steroid in orchiectomized (ORX) male mice, the origins of progesterone in males are unclear. To determine the origins of progesterone and androgens, we first determined the effect of ORX, adrenalectomy (ADX), or both (ORX+ADX) on progesterone levels in multiple male mouse tissues. As expected, intra-tissue androgen levels were mainly testicular-derived. Interestingly, progesterone levels remained high after ORX and ORX+ADX with the highest levels in white adipose tissue (WAT) and in the gastrointestinal tract. High progesterone levels were observed in mouse chow and exceptionally high progesterone levels were observed in food items such as dairy, eggs, and beef, all derived from female animals of reproductive age. To determine if orally ingested progesterone contributes to tissue levels of progesterone in males, we treated ORX+ADX and sham mice with isotope labeled progesterone or vehicle by oral gavage. We observed a significant uptake of labeled progesterone in WAT and prostate, suggesting that dietary progesterone may contribute to tissue levels of progesterone. In conclusion, although adrenal-derived progesterone contributes to intra-tissue progesterone levels in males, non-adrenal progesterone sources also contribute. We propose that dietary progesterone is absorbed and contributes to intra-tissue progesterone levels in male mice. We speculate that food with high progesterone content could be a significant source of progesterone in males, possibly with consequences for men undergoing androgen deprivation therapy for prostate cancer.

(459) Healthy Effects of Sex

Abstract Introduction Traditionally, sex has been thought of as a function predominantly exercised for reproductive purposes. Likely, religion and culture have both failed to promote a healthy appreciation for the pleasure that sex can provide. Due to the heavy focus on the reproductive utility of sex, society has perpetuated the misconception that increased age reduces libido. As such, the health benefits of sex, particularly in older adults, has been largely ignored as an integral part of preventative medicine. Furthermore, recent studies in the field of neuroendocrinology have demonstrated an increase in the number of receptors for estrogen, progesterone, and testosterone in different tissues of our body, especially in vital organs as brain, heart, bone, and muscle. Objective To spread awareness on the importance of maintaining a healthy amount of sexual activity in order to decrease adverse health outcomes. Methods In this study, we review the literature extensively and use the sexual histories of patients in our office to assess the beneficial health outcomes. Results We present evidence associating increased sexual activity with decreased risk of many disease states. Populations with higher frequency of arousal and orgasms showed reduced rates of breast cancer, prostate cancer, obesity, vaginal atrophy, dyspareunia, dysmenorrhea, dysfunctional uterine bleeding, recurrent urinary tract infections, urinary stress incontinence, fecal incontinence, genitourinary symptoms of menopause, abnormal false pap smears, vulvar, labial, and vaginal obliteration, and cardiovascular disease. Conclusions Our findings suggest that increased sexual activity is an important factor for the maintenance of general good health. These findings indicate decline in sexual activity, desire or function, particularly in older patients, as potential risk factors for adverse health outcomes. Promotion of healthy sexual behaviors have been strongly linked to sexual ability at advanced ages, with studies since 1948 showing that over 80% of women with orgasmic dysfunction do not masturbate, while over 80% of women who regularly achieve orgasm do not have trouble masturbating. Sexual literacy and comfort are key factors that may promote healthy sexual activity during adulthood. As such, masturbation should be promoted in adolescent and young adults as part of routine sexual education. Furthermore, standard medical practice should encourage regular sexual activity, with or without a partner. Disclosure No

Progesterone in gender-affirming therapy of trans women.

Progesterone is an endogenous steroid hormone with an important role for the physiology of the female reproductive system and the mammary gland. It has additional significant actions in other tissues, such as the cardiovascular system, the central nervous system, and bones. The present article explores potential clinical implications from the addition of bioidentical progesterone to gender-affirming treatment of trans women. For this purpose, it provides an overview of the physiological action of progesterone in target tissues and speculates on possible benefits for gender transitioning. Progesterone is expected to exert moderate anti-androgen action through suppression of the hypothalamic-pituitary-gonadal axis and inhibition of the conversion of testosterone to dihydrotestosterone. It may also contribute to breast maturation. In the long-term, progesterone could prevent bone loss and protect cardiovascular health. The potential benefits are mainly inferred by extrapolating evidence from biological actions in cisgender women and medical assumptions and hence, clinicians need to be cautious when applying these data into practice. Further research is needed to ascertain the efficacy and safety of progesterone in current hormonal regimens.

Comprehensive Sex Steroid Profiling in Multiple Tissues Reveals Novel Insights in Sex Steroid Distribution in Male Mice.

A comprehensive atlas of sex steroid distribution in multiple tissues is currently lacking, and how circulating and tissue sex steroid levels correlate remains unknown. Here, we adapted and validated a gas chromatography tandem mass spectrometry method for simultaneous measurement of testosterone (T), dihydrotestosterone (DHT), androstenedione, progesterone (Prog), estradiol, and estrone in mouse tissues. We then mapped the sex steroid pattern in 10 different endocrine, reproductive, and major body compartment tissues and serum of gonadal intact and orchiectomized (ORX) male mice. In gonadal intact males, high levels of DHT were observed in reproductive tissues, but also in white adipose tissue (WAT). A major part of the total body reservoir of androgens (T and DHT) and Prog was found in WAT. Serum levels of androgens and Prog were strongly correlated with corresponding levels in the brain while only modestly correlated with corresponding levels in WAT. After orchiectomy, the levels of the active androgens T and DHT decreased markedly while Prog levels in male reproductive tissues increased slightly. In ORX mice, Prog was by far the most abundant sex steroid, and, again, WAT constituted the major reservoir of Prog in the body. In conclusion, we present a comprehensive atlas of tissue and serum concentrations of sex hormones in male mice, revealing novel insights in sex steroid distribution. Brain sex steroid levels are well reflected by serum levels and WAT constitutes a large reservoir of sex steroids in male mice. In addition, Prog is the most abundant sex hormone in ORX mice.

Hormone receptor expression in aging mammary tissue and carcinoma from a rodent model after xenoestrogen disruption

AimsHormone receptors are the main markers applied for prognosis of breast cancer subtypes. Among modulators, exogenous chemical agents known as endocrine disruptors interact with certain receptors, triggering molecular pathways or increasing their expression. Bisphenol A (BPA), a xenoestrogen, interacts with several hormone receptors. Thus, our aim was to characterize the hormone receptor status in the mammary gland (MG) of aged female Mongolian gerbils exposed to BPA in pregnancy and lactation. MethodsWe evaluated the expression of receptors for estrogens (ERα and ERβ), progesterone (PR), prolactin (PRL-R), HER2/ErbB2, and androgen (AR) in normal and hyperplastic mammary tissue and in carcinomas developed after BPA exposure. Key findingsBPA-exposed MG presented increased ERα, whereas ERβ, PR, and PRL-R showed lower expression. AR and HER2/ErbB2 showed similar expression in normal and hyperplastic tissue from control, vehicle, and BPA groups. Both receptors were found in cytoplasm and nucleus in BPA-induced carcinoma. We demonstrate the presence of EZH2 expression, an epigenetic and epithelial-mesenchymal transition (EMT) marker, with a high H-score in BPA-exposed MG, which was associated with poor prognosis of cancer. Co-localization of ERα and EZH2 was present in normal and carcinoma features, corroborating the installation of ERα-positive mammary cancer associated with the EMT process. Enhanced EZH2 in BPA-exposed mammary tissue could decrease ERβ expression and promote tumorigenesis progress through HER2/ErbB2. SignificanceThe present study proposes the Mongolian gerbil as an experimental model for mammary carcinogenesis studies, based on BPA disruption that triggers a phenotype of increased ERα/HER2 positivity and depletion of ERβ/PR expression.

The Association between Dietary Inflammatory Index and Sex Hormones among Men in the United States.

This study investigated the association between Dietary Inflammatory Index and sex hormones in a large, nationally representative adult male sample. We utilized data from the 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey. Males aged ≥20 years who provided a 24-hour dietary intake history and underwent serum sex hormone testing were included in analysis. Weighted proportions and multivariable analysis controlling for age, race, energy, smoking status, education level, body mass index and time of venipuncture were used to evaluate the associations between Dietary Inflammatory Index and sex hormones. For 4,151 participants, Dietary Inflammatory Index ranged from -5.05 to 5.48. Mean±SD total testosterone was 419.30±176.27 ng/dl. Mean±SD total testosterone was lower among men in the highest tertile compared with men in the lowest tertile group (410.42±171.97 vs 422.71±175.69, p <0.001). A per unit increase in Dietary Inflammatory Index was related to 4.0% (95% CI 0.5-7.6) higher odds of testosterone deficiency. In the fully adjusted multivariable model, males in Dietary Inflammatory Index tertile 3 (the most pro-inflammatory) had 29.6% (3.1-63.0) higher odds of testosterone deficiency than those in tertile 1 (p trend=0.025). Interaction tests revealed no significant effect of body mass index on the association of Dietary Inflammatory Index with testosterone deficiency and all sex hormone parameters. Men adhering to a more pro-inflammatory diet appear to have a higher risk of testosterone deficiency, indicating the important role of diet in male reproductive health.

Altered prolactin and androgen receptors expression in companion rat benign mammary tumours.

Benign mammary tumours are among the most common tumours of companion rats (Rattus norvegicus domestica), as well as a major animal welfare concern and euthanasia. The first objective of this study was to evaluate the expression of oestrogen, progesterone, androgen, and prolactin receptors in neoplastic and normal mammary gland tissues and compare the expression of these receptors between groups. The second objective was to determine if the expression of these receptors in neoplastic mammary gland tissue correlates with overall survival and occurrence of an additional mass after initial mammary mass excision. The third objective was to determine if the expression of oestrogen, progesterone, androgen and prolactin receptors was associated with mammary tumor clinical parameters or with the age of the animals. Thirty-two benign mammary tumours were collected from companion rats and submitted for immunohistochemistry staining of prolactin receptor, oestrogen receptor alpha (ERa), progesterone and androgen receptors (AR). Allred score were obtained for mammary tumours (n=32) and surrounding normal mammary tissue (n=20) when present. Prolactin receptor expression increased significantly with mammary gland tumorigenesis (P < .0001), while AR expression decreased with tumorigenesis (P < .0001). Lower expression of ERa in tumor stroma was associated with shorter survival (P=.02). Hormonal receptor expression was not significantly associated with age, mass diameter, location nor likelihood of additional mass development. Further studies should investigate the effects of prolactin antagonists in a prospective study involving companion rats with benign mammary tumours.

Endocrine profiling of reproductive status and evidence of pseudopregnancy in the Pacific walrus (Odobenus rosmarus divergens).

Endocrine profiling is an increasingly utilized tool for detecting pregnancies in wild populations of mammals. Given the difficulty in calculating reproductive rates of Pacific walruses (Odobenus rosmarus divergens) the use of endocrine techniques for determining pregnancy rates could be particularly useful for management of the population. The goals of this study were to 1) determine if progesterone and total estrogen concentrations in ovarian tissues of female walruses could be used to determine reproductive state and 2) determine if walruses undergo a functional postpartum estrus, as is seen in other pinnipeds. Ovaries were collected from female walruses (n = 13) hunted in subsistence hunts by Alaska Native communities. Females were categorized as postpartum, full-term pregnant, pregnant diapause or unbred. Total estrogen concentrations were greatest in unbred (n = 2) and pregnant (n = 2) females. Progesterone concentrations were also nominally larger in unbred (n = 2) than pregnant (n = 2) and postpartum (n = 9) animals. Small samples sizes precluded the use of statistical comparisons among groups. Corpora lutea tissue samples in this study did not reflect the presence of a postpartum estrus in the month of May as postpartum females yielded lower total estrogen concentrations than unbred or pregnant animals. Both unbred animals were in a state of pseudopregnancy, which has not been physiologically described for this species before. The progesterone profiles in late (59 ng/g) and early (140 ng/g) pregnancy were lower than expected and fell within the range of the postpartum females (36–210 ng/g), suggesting low production of the hormone by the corpus luteum during these phases of pregnancy. Profiling reproductive hormones in free-ranging walruses demonstrates that an endocrine approach may be a valuable tool for determining reproductive status of females, however increased sample sizes and time of year must be considered to accurately separate pregnant versus pseudopregnant individuals.

Редкий случай реномедуллярной интерстициальной опухоли

Autopsy study of a 49-year-old patient demonstrates a rare kidney tumor that had a structure of a mesenchymal renomedullary interstitial tumor (RIO), which had specific characteristics. They include a predominance of the cellular component in the tumor, represented by cells with processes elements (fibroblasts, myofibroblasts), which were surrounded by collagen fibers of interstitium. Apparently, these cells can be involved in the regulation of renin and bicarbonates, the exchange of components of connective tissue (collagen fibers, proteoglycans) and hormones (estrogen, progesterone). Since these tumor cells regulate the synthesis and secretion of the substances, numerous clinical manifestations of RIO can be explained. Most likely, these include increased blood pressure, water-electrolyte disorders, hormonal disorders due to the presence of estrogen receptors, progesterone in the tumor tissue and metabolic disorders (diabetes mellitus). However, these assumptions require further clinical, morphological and immunohistochemical studies.

Selective Progesterone Receptor Modulators-Mechanisms and Therapeutic Utility.

Selective progesterone receptor modulators (SPRMs) are a new class of compounds developed to target the progesterone receptor (PR) with a mix of agonist and antagonist properties. These compounds have been introduced for the treatment of several gynecological conditions based on the critical role of progesterone in reproduction and reproductive tissues. In patients with uterine fibroids, mifepristone and ulipristal acetate have consistently demonstrated efficacy, and vilaprisan is currently under investigation, while studies of asoprisnil and telapristone were halted for safety concerns. Mifepristone demonstrated utility for the management of endometriosis, while data are limited regarding the efficacy of asoprisnil, ulipristal acetate, telapristone, and vilaprisan for this condition. Currently, none of the SPRMs have shown therapeutic success in treating endometrial cancer. Multiple SPRMs have been assessed for efficacy in treating PR-positive recurrent breast cancer, with in vivo studies suggesting a benefit of mifepristone, and multiple in vitro models suggesting the efficacy of ulipristal acetate and telapristone. Mifepristone, ulipristal acetate, vilaprisan, and asoprisnil effectively treated heavy menstrual bleeding (HBM) in patients with uterine fibroids, but limited data exist regarding the efficacy of SPRMs for HMB outside this context. A notable class effect of SPRMs are benign, PR modulator-associated endometrial changes (PAECs) due to the actions of the compounds on the endometrium. Both mifepristone and ulipristal acetate are effective for emergency contraception, and mifepristone was approved by the US Food and Drug Administration (FDA) in 2012 for the treatment of Cushing’s syndrome due to its additional antiglucocorticoid effect. Based on current evidence, SPRMs show considerable promise for treatment of several gynecologic conditions.

Role of Melatonin in Breast Carcinoma: Correlation of Expression Patterns of Melatonin-1 Receptor With Estrogen, Progesterone, and HER2 Receptors.

Breast carcinoma is a multifaceted-etiology malignancy. The presence of estrogen (ER), progesterone (PR), and HER2 (human epidermal growth factor receptor 2) receptors in breast carcinoma tissue has therapeutic implications. Recent studies indicate that pineal hormone melatonin by its receptor melatonin 1 (MT1) also influences the development and growth of breast cancer cells. The aim of this cross-sectional study was to elucidate the expression pattern of MT1 receptor in relation to estrogen, progesterone, and HER2 receptors in breast carcinoma. Two groups (receptor positive and triple negative) of breast carcinoma were taken. For comparison, normal mammary tissue was used as control. Immunohistochemistry was carried out using anti-melatonin receptor 1A antibody. Membranous/cytoplasmic expression was seen more than the nuclear expression in the cancerous tissue. Positive correlation of the MT1 expression was seen with ER, PR, and HER 2 receptor. Higher MT1 receptor expression was seen in the receptor-positive cases in comparison with triple-negative cases, which might signify melatonin deficiency in the former, leading to reactive increase in cell receptors. No correlation of MT1 expression with Ki67 index or lymph node status in both receptor-positive and triple-negative cases was found. Normal mammary tissue mainly showed cytoplasmic MT1 immunoreactivity of epithelial cells (ducts and acini), myoepithelial cells, and lining epithelium of blood vessels. Receptor-positive cases would, therefore, benefit from the use of melatonin as supporting therapy. This indicates that melatonin receptor status can be used as an independent pathologic indicator to evaluate breast carcinoma tissue, and melatonin receptor status may help to determine treatment protocols.

The Effect of Rutin on Progesterone and Estrogen Receptor Expression in Uterine Endometrial Tissue in the Heterotopic Transplantation of Newborn Mouse Ovary

Background: Rutin (quercetin-3-rhamnosyl-glucoside), a flavonoid, is derived from plants and has antioxidant properties. Objectives: This study aimed to evaluate the effect of different concentrations of rutin on mouse ovary heterotopic allotransplantation. Methods: The present animal experimental study was conducted on 40 female adult Balb/c mice weighing 30 ± 5 g at the Jundishapur University of Medical Sciences, Ahvaz, Iran, during 2016 - 2018. The mice were divided by permuted block randomization into 8 groups (n = 5): OVX (ovariectomy), as the negative control; normal (positive control); OVX + OVA (ovariectomy and transplantation) (control), treated with 0.5 mL of normal saline; OVX + OVA + 10 mg/kg of rutin; OVX + OVA + 30 mg/kg of rutin; OVX + OVA + 60 mg/kg of rutin; OVX + OVA + 100 mg/kg of rutin; and the autograft. Groups were treated daily. Fourteen days after transplantation, ovarian grafts were collected and processed histologically for follicle number counting. Serum estrogen (E2) and progesterone (P4) levels were evaluated. Furthermore, the expression of Estrogen Receptor alpha (ERα), Estrogen Receptor beta (ERβ), and Progesterone Receptor (PR) in the uterine endometrial tissue was tested using qRT-PCR and western blotting. Results: A decrease in the number of mature follicles and increase in the number of atretic follicles (mean ± SD: OVX + OVA + 30 = 19.00 ± 1.000, OVX + OVA + 60 = 25.00 ± 5.000, and OVX + OVA + 100 = 23.00 ± 2.646) were observed in all groups treated with rutin in comparison with the control group (mean ± SD: 12.33 ± 2.517) (P value < 0.05). The level of E2 and P4 (mean ± SD: OVX + OVA + 100 = 6.133 ± 1.026) increased in comparison with the OVX + OVA group (mean ± SD: 0.4667 ± 0.2517) (P value < 0.05). The protein expression of ERα (mean ± SD: OVX + OVA + 10 = 1.615 ± 0.1701 and OVX + OVA + 30 = 1.744 ± 0.1779) in comparison with the control group (mean ± SD: 0.7089 ± 0.1131), and ERβ (mean ± SD: OVX + OVA + 10 = 0.7747 ± 0.4365, OVX + OVA + 30 = 0.9220 ± 0.1245, OVX + OVA + 60 = 0.7701 ± 0.2150, and OVX + OVA + 100 = 0.6676 ± 0.1547) increased in a dose-dependent manner in all groups treated with rutin in comparison with the OVX + OVA group (mean ± SD: 0.1534 ± 0.06109) (P value < 0.05). No significant changes in PR were found in groups treated with rutin in comparison with the control group. Conclusions: The results of the present study indicated that rutin increases E2 and P4 levels in ovarian hetero allograft mice. Rutin also upregulated the expression of ERα and ERβ but had no significant effect on PR.

Steroidogenesis and the initiation of parturition

Overview. One of the most fundamental axioms of mammalian reproduction is that pregnancy requires the support of progesterone without which it cannot be established or maintained. Though this basic physiological tenet was accepted long ago, major gaps in our understanding of the physiology of both pregnancy and parturition remain which hamper our ability to solve clinically and agriculturally significant problems such as low fertility, fetal growth restriction, preterm birth and poor neonatal outcomes. The historical reliance of our understanding of both pregnancy and parturition on this single hormone, and how it has been measured in the vast majority of studies, may represent a tangible weakness and impediment to progress. Other weaknesses include a desire to fit all species into a unified paradigm, and a reluctance to accept that physiological processes regulated by progesterone or other progestins in different tissues might vary in reliance on classic (nuclear receptor) versus other, non-classical mechanisms of action. The relative importance of these distinct response pathways in certain cells or tissues also may differ across species, as does so much of basic reproductive physiology. It is well known that certain species are reliant on luteal function throughout gestation, whereas the placenta subsumes endocrine support in others (Geisert & Conley 1998), yet progesterone alone is still believed to be the single common element. As radical as it might seem, however, progesterone may not be the single common hormone of pregnancy in mammals.

Efficacy of carprostol tromethamine combined with mifepristone in the treatment of uterine fibroids

【Abstract】Objective: To investigate the clinical efficacy of carboprost tromethamine combined with mifepristone in the treatment of uterine fibroids. METHODS: A total of 66 patients with uterine fibroids admitted to our hospital between April 2018 and January 2019 were selected as subjects. According to the two different treatment methods, patients were divided equally. The observation group and the control group, each group of 33 people. The oxytocin drug treatment was medicated to the control group, and the prostaglandin tromethamine combined with mifepristone was medicated to the observation group. The treatment effect, adverse reaction, operation, and uterine muscle before and after surgery were observed in these two groups. Tumor tissue progesterone receptor and estrogen receptor levels. Results: The clinical treatment effect of the observation group was 93.94%, and the clinical treatment effect of the control group was 60.61%. The clinical treatment effect of the observation group was significantly higher than that of the control group; also the incidence of adverse reactions in the observation group in terms of rash, fatigue, nausea and vomiting was much lower than the control group, and could observe a significant difference. Finally in observation group, the amount of intraoperative blood loss, operation time and hospitalization time were better than those of the control group. The progesterone receptor and estrogen receptor levels in the uterine fibroid tissue after surgery should also be better than the control group, it is worth to make further comparison. Conclusion: Carprostol tromethamine combined with mifepristone is effective in the treatment of uterine fibroids and can be further developed.