Hormone Sensitivity Research Articles

Incidental resection of a scrotal aggressive angiomyxoma mimicking a spermatocele: a case report

Aggressive angiomyxoma is a rare mesenchymal neoplasm, occurring mainly in females. It is located in the pelvis and perineum, with known metastasis and hormone sensitivity only in females. Local recurrence is relatively common. We describe the case of a 62-year-old man who presented with symptoms and signs of a spermatocele. Scrotal exploration with surgical excision of the lesion was done. Because a benign setting was assumed, no radical inguinal orchiectomy was performed. The specimen sent to pathology confirmed an aggressive angiomyxoma with positive resection margins. Despite the plurality of benign scrotal masses such as spermatoceles or hydroceles, rare neoplasms should always be kept in mind. Hence, complete excision should be performed whenever possible. We selected an active surveillance strategy despite positive margins, since there is no described case of metastasis in men to date. Therefore, regular scrotal ultrasound examinations every 3 months were arranged as follow-up.

Correction to: a Phase 2 Study of 16α-[18F]-Fluoro-17β-Estradiol Positron Emission Tomography (FES-PET) as a Marker of Hormone Sensitivity in Metastatic Breast Cancer (MBC).

Two data points from Table 1. (continued) were published in error. The corrected data in Table 1. (continued) are shown, in italic, below.

Histone demethylase KDM7A controls androgen receptor activity and tumor growth in prostate cancer.

Prostate cancer can be controlled by androgen-hormone treatment until the cancer becomes refractory. It is believed that hormone sensitivity is largely dependent on androgen receptor (AR) activity. Here, we found the histone demethylase KDM7A which demethylates histone H3K27 to be overexpressed in enzalutamide resistant castration-resistant prostate cancer cell line C4-2b, and investigated the molecular mechanism whereby androgen receptor activity is regulated by KDM7A. We engineered AR-positive LNCaP cells to stably express a short-hairpin RNA against KDM7A mRNA from a lentiviral vector. By measuring AR downstream gene expression after androgen stimulation, we found that a KDM7A-deficient cell line showed lower AR downstream gene expression compared to a control cell. KDM7A knock-down in LNCaP cell line caused decreased cell proliferation. Western blot analysis with modified-histone antibody revealed that the KDM7A-knock-down LNCaP cell line had increased H3K27 di-methylation. We confirmed KDM7A binding on AR target-gene promoters after hormone stimulation in chromatin-immunoprecipitation experiments. And increased H3K27 di-methylation was observed in KDM7A knock-down LNCaP stable cell. Treatment with KDM7A inhibitor, TC-E 5002, reduced proliferation and induced apoptosis of prostate cancer cells. Finally, we observed that the KDM7A protein was significantly upregulated in prostate cancer tissue, and that this difference correlated with the Gleason score. These data suggested that KDM7A is potentially a good therapeutic target for prostate cancer drugs and can be used as potentially a good prognostic indicator for prostate cancer and related treatment strategies.

Suicide Risk and the Menstrual Cycle: a Review of Candidate RDoC Mechanisms.

Risk for suicidal behavior may fluctuate across the menstrual cycle. Here, we use the RDoC framework to review potential mechanisms by which the cycle may increase acute suicide risk. The menstrual cycle impacts the majority of RDoC constructs linked to suicide risk, particularly among hormone-sensitive women, such as those with premenstrual dysphoric disorder or premenstrual exacerbation of a psychiatric disorder. Despite this, there are no published studies examining suicidal ideation, planning, or behavior longitudinally across the cycle. More work is needed to understand how hormone sensitivity may relate to both trait and state suicide risk. Intensive multilevel investigations of cyclical hormone effects on suicide risk through specific RDoC mechanisms are suggested. This is a fertile research area and may provide key insights regarding the mechanisms of acute suicide risk.

Comparative Study of Vitamin D Deficiency between PCOD and Normal Women: A Prospective Hospital Based Study

Background: - Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, with a prevalence of 6–10% in the general population. PCOS is characterized by the following: ovulatory dysfunction resulting in oligo-amenorrhea and/or anovulation, hyperandrogenism and/or hirsutism and the presence of polycystic ovarian morphology by ultrasound. Vitamin D also plays a physiologic role in reproduction including ovarian follicular development and luteinization via altering anti- Mullerian hormone (AMH), signaling, follicle- stimulating hormone sensitivity and progesterone production in human granulosa cells. The aim of this study aimed to compare levels of vitamin D in women with PCOS and normal women. Methodology: - Total fifty women were included in this study. Among the fifty cases 50% were from PCOD group and 50% were normal. This study were conducted in the Dept. of Obs/Gynae, Madhubani Medical College, Bihar. Blood sample was taken and serum vitamin D concentration was measured. Result: - Mean serum 25(OH) vitamin-D level in PCOD group and in control group is clinically significant.Conclusion: - This study concludes that 25(OH) vitamin-D was clinically significant, but not sufficient to be a diagnostic tool for PCOS.

Light, Ethylene and Auxin Signaling Interaction Regulates Carotenoid Biosynthesis During Tomato Fruit Ripening.

Light signaling and plant hormones, particularly ethylene and auxins, have been identified as important regulators of carotenoid biosynthesis during tomato fruit ripening. However, whether and how the light and hormonal signaling cascades crosstalk to control this metabolic route remain poorly elucidated. Here, the potential involvement of ethylene and auxins in the light-mediated regulation of tomato fruit carotenogenesis was investigated by comparing the impacts of light treatments and the light-hyperresponsive high pigment-2 (hp2) mutation on both carotenoid synthesis and hormonal signaling. Under either light or dark conditions, the overaccumulation of carotenoids in hp2 ripening fruits was associated with disturbed ethylene production, increased expression of genes encoding master regulators of ripening and higher ethylene sensitivity and signaling output. The increased ethylene sensitivity observed in hp2 fruits was associated with the differential expression of genes encoding ethylene receptors and downstream signaling transduction elements, including the downregulation of the transcription factor ETHYLENE RESPONSE FACTOR.E4, a repressor of carotenoid synthesis. Accordingly, treatments with exogenous ethylene promoted carotenoid biosynthetic genes more intensively in hp2 than in wild-type fruits. Moreover, the loss of HP2 function drastically altered auxin signaling in tomato fruits, resulting in higher activation of the auxin-responsive promoter DR5, severe down-regulation of AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) genes and altered accumulation of AUXIN RESPONSE FACTOR (ARF) transcripts. Both tomato ARF2 paralogues (Sl-ARF2a and SlARF2b) were up-regulated in hp2 fruits, which agrees with the promotive roles played by these ARFs in tomato fruit ripening and carotenoid biosynthesis. Among the genes differentially expressed in hp2 fruits, the additive effect of light treatment and loss of HP2 function was particularly evident for those encoding carotenoid biosynthetic enzymes, ethylene-related transcription factors, Aux/IAAs and ARFs. Altogether, the data uncover the involvement of ethylene and auxin as part of the light signaling cascades controlling tomato fruit metabolism and provide a new link between light signaling, plant hormone sensitivity and carotenoid metabolism in ripening fruits.

Switch from abiraterone plus prednisone to abiraterone plus dexamethasone at asymptomatic PSA progression in patients with metastatic castration-resistant prostate cancer.

To evaluate the effects of switching from prednisone (P) to dexamethasone (D) at asymptomatic prostate-specific antigen (PSA) progression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). Among 93 patients treated with AA between January 2013 and April 2016 in our institution, 48 consecutive asymptomatic patients with mCRPC, who experienced biochemical progression on treatment with AA+P 10 mg/day, were included. A corticosteroid switch to AA+D 0.5 mg/day at PSA increase was administered until radiological and/or clinical progression. The primary endpoint was progression-free-survival (PFS). A prognostic score based on independent prognostic factors was defined. The median time to PSA progression on AA+P was 8.94 months. The median PFS on AA+D and AA+corticosteroids (P then D) was 10.35 and 20.07 months, respectively. A total of 56.25% of patients showed a decrease or stabilization in PSA levels after the switch. In univariate analysis, three markers of switch efficiency were significantly associated with a longer PFS: long hormone-sensitivity duration (≥5 years; median PFS 16.62 vs 4.17 months, hazard ratio [HR] 0.30, 90% confidence interval [CI] 0.16-0.56); low PSA level at the time of switch (<50 ng/mL; median PFS 15.21 vs 3.86 months, HR 0.33, 90% CI 0.18-0.60); and short time to PSA progression on AA+P (<6 months; median PFS 28.02 vs 6.65 months, HR 0.41 (90% CI 0.21-0.81). In multivariate analysis, hormone sensitivity duration and PSA level were independent prognostic factors. A steroid switch from P to D appears to be a safe and non-expensive way of obtaining long-term responses to AA in selected patients with mCRPC. A longer PFS has been observed in patients with previous long hormone sensitivity duration, and/or low PSA level and/or short time to PSA progression on AA+P.

Mouse ER+/PIK3CAH1047R breast cancers caused by exogenous estrogen are heterogeneously dependent on estrogen and undergo BIM-dependent apoptosis with BH3 and PI3K agents.

Estrogen dependence is major driver of ER + breast cancer, which is associated with PI3K mutation. PI3K inhibition (PI3Ki) can restore dependence on ER signaling for some hormone therapy-resistant ER + breast cancers, but is ineffective in others. Here we show that short-term supplementation with estrogen strongly enhanced Pik3caH1047R-induced mammary tumorigenesis in mice that resulted exclusively in ER + tumors, demonstrating the cooperation of the hormone and the oncogene in tumor development. Similar to human ER + breast cancers that are endocrine-dependent or endocrine-independent at diagnosis, tumor lines from this model retained ER expression but were sensitive or resistant to hormonal therapies. PI3Ki did not induce cell death but did cause upregulation of the pro-apoptotic gene BIM. BH3 mimetics or PI3Ki were unable to restore hormone sensitivity in several resistant mouse and human tumor lines. Importantly however, combination of PI3Ki and BH3 mimetics had a profound, BIM-dependent cytotoxic effect in PIK3CA-mutant cancer cells while sparing normal cells. We propose that addition of BH3 mimetics offers a therapeutic strategy to markedly improve the cytotoxic activity of PI3Ki in hormonal therapy-resistant and ER-independent PIK3CA-mutant breast cancer.

Electrophysiological properties of medium spiny neurons in the nucleus accumbens core of prepubertal male and female Drd1a-tdTomato line 6 BAC transgenic mice.

The nucleus accumbens core (AcbC) is a striatal brain region essential for integrating motivated behavior and reward processing with premotor function. In humans and rodents, research has identified sex differences and sex steroid hormone sensitivity in AcbC-mediated behaviors, in disorders, and in rats in the electrophysiological properties of the AcbC output neuron type, the medium spiny neuron (MSN). It is unknown whether the sex differences detected in MSN electrophysiological properties extend to mice. Furthermore, MSNs come in distinct subtypes with subtle differences in electrophysiological properties, and it is unknown whether MSN subtype-specific electrophysiology varies by sex. To address these questions, we used male and female Drd1a-tdTomato line 6 bacterial artificial chromosome transgenic mice. We made acute brain slices of the AcbC, and performed whole cell patch-clamp recordings across MSN subtypes to comprehensively assess AcbC MSN subtype electrophysiological properties. We found that ( 1 mice MSNs did not exhibit the sex differences detected in rat MSNs, and 2) electrophysiological properties differed between MSN subtypes in both sexes, including rheobase, resting membrane potential, action potential properties, intrinsic excitability, input resistance in both the linear and rectified ranges, and miniature excitatory postsynaptic current properties. These findings significantly extend previous studies of MSN subtypes performed in males or animals of undetermined sex and indicate that the influence of sex upon AcbC MSN properties varies between rodent species. NEW & NOTEWORTHY This research provides the most comprehensive assessment of medium spiny neuron subtype electrophysiological properties to date in a critical brain region, the nucleus accumbens core. It additionally represents the first evaluation of whether mouse medium spiny neuron subtype electrophysiological properties differ by sex.

Interpreting biological variation: seeds, populations and sensitivity thresholds

AbstractSeeds offer a unique perspective from which to view biology. An individual seed is an autonomous biological entity that must rely on its own resources (and resourcefulness) to persist after dispersal and to time its transition to germination and seedling growth to coincide with environmental opportunities for survival. At the same time, seed biology in agriculture and ecology is determined largely by the behaviours of populations of individual seeds. The percentage of seeds in a population that is in a particular state (e.g. dormant, germinated, dead) at a given time is a fundamental metric of seed biology. This duality of individual diversity underlying consistent population-wide behaviour patterns can be described quantitatively using population-based threshold (PBT) models. While conceptually simple, these models are highly flexible and can describe the wide diversity of responses of seed populations to temperature, water potential, hormones, oxygen, light, ageing and combinations of these factors. This seed behaviour is linked to respiratory rates of individual seeds, indicating that basic metabolic processes within seeds vary among individuals in accordance with PBT principles. Looking more broadly across microbial, plant and animal biology, examples of cellular diversity in hormonal sensitivity, gene expression, developmental responses and signalling abound. This variation often is termed ‘noise’, and analysis efforts are focused on extracting mean signals from this variation to understand regulatory pathways. However, extension of the PBT approach to the cellular and molecular levels suggests that population sensitivity distributions and recruitment phenomena may underlie many fundamental biological processes. Thus, concepts and quantitative approaches developed for the analysis of seed populations can be applied across biological scales from molecules to ecosystems to interpret inherent biological variation and provide mechanistic insights into the nature of biological regulatory systems.

In Silico Investigation of the Pharmacological Mechanisms of Beneficial Effects of Ginkgo biloba L. on Alzheimer's Disease.

Based on compelling experimental and clinical evidence, Ginkgo biloba L. exerts a beneficial effect in ameliorating mild to moderate dementia in patients with Alzheimer’s disease (AD) and other neurological disorders, although the pharmacological mechanisms remain unknown. In the present study, compounds, their putative target proteins identified using an inverse docking approach, and clinically tested AD-related target proteins were systematically integrated together with applicable bioinformatics methods in silico. The results suggested that the beneficial effects of G. biloba on AD may be contributed by the regulation of hormone sensitivity, improvements in endocrine homeostasis, maintenance of endothelial microvascular integrity, and proteolysis of tau proteins, particularly prior to amyloid β-protein (Aβ) plaque formation. Moreover, we identified six putative protein targets that are significantly related to AD, but have not been researched or have had only preliminary studies conducted on the anti-AD effects of G. biloba. These mechanisms and protein targets are very significant for future scientific research. In addition, the existing mechanisms were also verified, such as the reduction of oxidative stress, anti-apoptotic effects, and protective effects against amyloidogenesis and Aβ aggregation. The discoveries summarized here may provide a macroscopic perspective that will improve our understanding of the molecular mechanism of medicinal plants or dietary supplements, as well as new clues for the future development of therapeutic strategies for AD.

Endospanin-2 enhances skeletal muscle energy metabolism and running endurance capacity.

Metabolic stresses such as dietary energy restriction or physical activity exert beneficial metabolic effects. In the liver, endospanin-1 and endospanin-2 cooperatively modulate calorie restriction-mediated (CR-mediated) liver adaptations by controlling growth hormone sensitivity. Since we found CR to induce endospanin protein expression in skeletal muscle, we investigated their role in this tissue. In vivo and in vitro endospanin-2 triggers ERK phosphorylation in skeletal muscle through an autophagy-dependent pathway. Furthermore, endospanin-2, but not endospanin-1, overexpression decreases muscle mitochondrial ROS production, induces fast-to-slow fiber-type switch, increases skeletal muscle glycogen content, and improves glucose homeostasis, ultimately promoting running endurance capacity. In line, endospanin-2-/- mice display higher lipid peroxidation levels, increased mitochondrial ROS production under mitochondrial stress, decreased ERK phosphorylation, and reduced endurance capacity. In conclusion, our results identify endospanin-2 as a potentially novel player in skeletal muscle metabolism, plasticity, and function.

Sarcopenia: assessment of disease burden and strategies to improve outcomes.

Life expectancy is increasing worldwide, with a resultant increase in the elderly population. Aging is characterized by the progressive loss of skeletal muscle mass and strength – a phenomenon called sarcopenia. Sarcopenia has a complex multifactorial pathogenesis, which involves not only age-related changes in neuromuscular function, muscle protein turnover, and hormone levels and sensitivity, but also a chronic pro-inflammatory state, oxidative stress, and behavioral factors – in particular, nutritional status and degree of physical activity. According to the operational definition by the European Working Group on Sarcopenia in Older People (EWGSOP), the diagnosis of sarcopenia requires the presence of both low muscle mass and low muscle function, which can be defined by low muscle strength or low physical performance. Moreover, biomarkers of sarcopenia have been identified for its early detection and for a detailed identification of the main pathophysiological mechanisms involved in its development. Because sarcopenia is associated with important adverse health outcomes, such as frailty, hospitalization, and mortality, several therapeutic strategies have been identified that involve exercise training, nutritional supplementation, hormonal therapies, and novel strategies and are still under investigation. At the present time, only physical exercise has showed a positive effect in managing and preventing sarcopenia and its adverse health outcomes. Thus, further well-designed and well-conducted studies on sarcopenia are needed.

P311 Modulates Adipocyte Development

Adipogenesis is a complex process of adipocytes formed from progenitor cells that involves changes in gene expression, cell morphology and hormone sensitivity. The differentiation of adipocytes is regulated by a well‐orchestrated network of transcriptional factors and associated cell signaling proteins responsible for adipocyte development and maturation. An in‐depth understanding of adipogenesis is essential to fight against metabolic disorders including obesity. Our lab investigates the P311 protein that plays a key role in adipocyte development. P311 has been shown to play an essential role in blood pressure regulation and vascular contractility (Badri et al., J Clin Inv 2013). In this study, we evaluate the adipogenic function of P311 using NIH3T3‐L1 cell culture model and genetically modified animal models. We show that P311 expression, initiated with the induction of adipogenesis in 3T3‐L1 cells, increased during the adipogenesis process. Additionally, siRNA mediated P311 knockdown inhibited adipogenic differentiation in 3T3‐L1 cells. The increase in P311 expression during adipogenesis correlated with the increase in the expression of key adipogenic transcriptional factors PPARγ2 and C/EBPα. Further, we observed nuclear localization of P311 in immunofluorescence studies indicating potential transcriptional regulatory/co‐regulatory function/s of P311. To verify the transcriptional regulatory/co‐regulatory functions of P311, we conducted chromatin immunoprecipitation (ChIP) assays using adipogenesis induced 3T3‐L1 cells transfected with pCMV‐P311 or an empty vector, pCMV. P311 overexpressing adipocytes demonstrated the recruitment of P311 to the PPARγ2 promoter regions (~800 fold) compared to empty vector transfected adipocytes. However, P311 immunocomplexes failed to amplify C/EBPα promoter. Further, to verify the involvement of P311 in adipose tissue development, we conducted animal studies and did not find any differences in the white fat weights (gonadal and subcutaneous fat) between wild type mice (WT) and P311 knockout mice (KO) (18–21 weeks). However, we observed an increase in the numbers of LipidTox stained adipocytes as detected in fluorescenceactivated cell sorting (FACS) analysis in white fat of WT mice than P311 KO mice. Our current studies demonstrate the critical role of P311 in adipocyte development through the transcriptional regulation of PPARγ2.Support or Funding InformationThis study is supported by grant funds from NIMHD/NIH (U54MD008621 to Hampton University and S21MD000101).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract P6-04-02: CDK6 might be a key factor for efficacy of CDK4/6 inhibitor and the hormone sensitivity following acquired resistance

Abstract Background: CDK4/6 inhibitors have received FDA breakthrough therapy designation as 1st line treatment for advanced estrogen receptor positive breast cancer patients. However, the benefit offered by CDK4/6 inhibitors is individually different and furthermore acquired resistance to the drugs is monumental challenges. It is urgent need to search for the biomarker and understand the drug sensitivity and its alteration after acquired resistance. Results: To identify the efficacy of CDK4/6 inhibitors, we assessed IC50 of ribociclib in several cell lines. Luminal cell lines (MCF-7, T-47D) exhibited lower ribociclib IC50 than HER-2 (SK-BR-3) and triple negative cell lines (MDA-MB-231, BT-20). Immunoblot analysis of Luminal cell lines showed extremely lower levels of CDK6 compared with others. CDK6-transfected MCF-7 by means of expression vector reduced the sensitivity equivalent to MDA-MB-231 not only to ribociclib but also to palbociclib and abemaciclib. Protein level of ERα in CDK6-transfected MCF-7 stayed unchanged and fulvestrant sensitivity was unaltered as well. Subsequently, we detect the efficacy of ribociclib in hormone resistant cell lines. Estrogen deprivation-resistant (EDR) cells (EDR1:ER-positive, EDR2:ER-negative) and fulvestrant resistance (MFR) cells (loss of ER expression) established from MCF-7 maintained ribocilib sensitivity to the same degree with MCF-7. No marked difference in IC50 was observed between EDR1/2 and MFR, and CDK6 expressions were comparable to MCF-7. These results suggest that high level of CDK6 expression weaken the sensitivity to CDK4/6 inhibitors. The inhibitors would provide more effective benefits to tumors expressing lower level of CDK6 than the higher, independent of hormone sensitivity. To understand the characteristics in acquired resistance, ribociclib resistant cell lines (RIBR1/2) were established from EDR1 by long-term culture with ribociclib. RIBR designed lower level of p21, p27 and ERα by immunoblot analysis. EDR1 were promoted cell growth by estrogen addition, while RIBR were not. Further, ER activity of RIBR was intensely decreased, and mRNA levels of the ER target genes, PgR and EGR3 were also decreased. Therefore, the responsiveness to tamoxifen and fulvestrant were lost. On the other hand, PI3K inhibitor and mTOR inhibitor suppressed cell growth to the same extent as EDR1, suggesting that RIBR were reduced ER dependence and remain reliant on PI3K/Akt/mTOR pathway. Conclusion: The possibility of CDK6 as a biomarker is corroborated by the finding that low level of CDK6 expression is positively correlated with the efficacy of CDK4/6 inhibitor. Further ER dependence had decreased after acquired CDK4/6 inhibitor resistance whereas the dependence on PI3K/Akt/mTOR pathway still remain, indicating the inhibition of PI3K/Akt/mTOR pathway would be amenable to therapeutic target. Citation Format: Iida M, Nakamura M, Tokuda E, Niwa T, Ishida T, Hayashi S-I. CDK6 might be a key factor for efficacy of CDK4/6 inhibitor and the hormone sensitivity following acquired resistance [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-04-02.

Fertility preservation in endometrial carcinoma: Case series of 11 patients

Introduction: Endometrial cancer comprises 7.1% of all new cancer cases in females. Carcinoma of the endometrium is one of the long-term complications of polycystic ovarian syndrome (PCOS) due to unopposed estrogen action due to chronic anovulation. The standard treatment involves hysterectomy and bilateral salpingo-oophorectomy, due to its hormonal sensitivity. In endometrial cancer without infiltration to the myometrium and no extrauterine involvement, conservative treatment can be offered to women who wish to preserve fertility. Results: We report 11 cases of endometrial carcinoma either diagnosed during workup for infertility or referred for fertility preservation (FP) before definitive treatment. About 72.7% (7/11) of patients had PCOS, it becomes important for clinicians to suspect and rule out endometrial carcinoma by regular endometrial surveillance which, includes transvaginal ultrasound and/or endometrial biopsy in all PCOS women who have abnormal uterine bleeding, prolonged amenorrhea, unopposed estrogen exposure, and thick endometrium especially on day 3 of the menstrual cycle. About 36.36% (4/11) of our patients were not convinced for FP and were either lost to follow-up or underwent definitive therapy. Thus, it is important that all patients with endometrial carcinoma should be counseled not only by the oncologist but also by a reproductive endocrinologist and a psychosocial counselor, both together and separately. This will enable the patient to make a right choice of the treatment modality. Conclusion: Conservative treatment with progestogen therapy in selected young patients with well-differentiated carcinoma limited to the endometrium helps in preserving fertility. If they fail to conceive in the first attempt of in vitro fertilization, it is mandatory to monitor them for recurrence till a definitive treatment is planned. If definitive treatment is required fertility can be preserved either by oocyte or embryo freezing. Some women with low risk of ovarian involvement can benefit by ovarian tissue cryopreservation.

Common transcriptional regulation of ABA and ethylene

Plant hormones are versatile chemical regulators of plant growth. The concept of hormone ‘interaction’[1] has gained much importance and several key players of hormonal network are uncovered for major plant hormones. The fact that hormones are structurally unrelated and their interaction elicits different genomic and non-genomic responses suggest hormone interaction involve co-regulation at multiple levels [2]. Recent studies suggest that hormonal interaction involves control over biosynthesis genes [3-6], key components of signalling pathways [7, 8], hormone distribution [9, 10], and interaction at the level of gene expression [11-13]. The spatial and temporal changes in hormone sensitivity add further complexity as they are developmental stagedependent [14]. Understanding how these mechanisms are integrated would allow us to manipulate hormone interaction-regulated growth response under environmental changes. One such prominent emerging hormone interaction is ethylene and abscisic acid (ABA) in several growth processes. In this short review, I discuss some of the common transcriptional regulators of ethylene and ABA.

Assessment of Vitamin D Levels in Women with Polycystic Ovarian Syndrome

Background: polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, with a prevalence of 6–10% in the general population. PCOS is characterized by the following: ovulatory dysfunction resulting in oligo-amenorrhea and/or anovulation, hyperandrogenism and/or hirsutism and the presence of polycystic ovarian morphology by ultrasound. Vitamin D also plays a physiologic role in reproduction including ovarian follicular development and luteinization via altering anti-Mullerian hormone (AMH), signaling, follicle-stimulating hormone sensitivity and progesterone production in human granulosa cells. Aim of the Work: this study aimed to compare levels of vitamin D in women with PCOS and healthy fertile women. Patient and Methods: this case control study was conducted in Ain Shams Maternity hospital in outpatient infertility clinics and family planning clinic during the period from March 2017 to October 2017. It was included 40 women diagnosed with PCOS based on Rotterdam criteria and 40 fertile women without PCOS who were recruited from family planning clinic. Results: 25(OH) vitamin-D level was significantly lower in PCOS group than in the control group. Conclusion: 25(OH) vitamin-D was significantly lower in PCOS group than in the control group, but not sufficient to be a diagnostic tool for PCOS. Recommendation: larger studies are still needed to clarify the rule of vitamin D in infertility.

ASSOTIATIONS OF PECULIARITIES OF HLA-PHENOTYPE AND THE SENSIBILITY TO THE CORTICOSTEROID TREATMENT IN PATIENTS WITH CHRONIC GLOMERULONEPHRITIS WITH NEPHROTIC SYNDROME

The purpose of study was determination of HLA -antigens I and II classes as predictors of ineffectiveness of initial steroid therapy, and according prognozonegative markers of chronic glomerulonephritis with nephrotic syndrome.&#x0D; Methods. In 59 chronic glomerulonephritis with nephrotic syndrome patients (steroid sensitive n=33 (1 gr.) and steroid resistant’s n= 26 (2 gr.)) and 350 healthy donors( control group) studied HLA antigens I and II classes of the special anti- HLA-antigens panel (20 antigens of locus A, 31 – of locus B and 9- of locus DR).&#x0D; Result. In patients with chronic glomerulonephritis, nephrotic syndrome with hormone sensitivity relative risk is high at the presents of A28 (RR=8,5, r р &lt;0,001), it made attributive risk (=0,37). In comparison with a control group, RR&gt;2 for antigens A11 (RR=2,23), A23 (RR=4,28), A24 (RR=3,3), A29 (RR=10,78) that A30 (RR=11,23); attributive risk more than 0,1 for the antigen A11 (=0,16) ; A24&#x0D; (=0,13), other did not differ from control. Subzero connection is exposed for the antigens of A2 (р&lt;0,001), А9 (р=0,007). In locus antigen B14 (RR=5,65, р =0,001) are exposed, B44 (RR=48,25, р =0,004), B51(RR=12,32, р =0,006) and attributive risk of development of disease (according =0,24, 0,12 ; 0,14); and antigens B38 and B41 (RR=11,57, р=0,05). The steroid sensitivity was associated with the antigens B5 (p=0,033), B12 (p=0,005) and B35 (p=0,021). In locus DR made etiologic faction antigens DR4 (RR=7,0 and =0,24) DRw52 (RR=7,0 and =0,25).&#x0D; Conclusions. For patients with chronic glomerulonephritis with a nephrotic syndrome antigens of HLA-B14,B38, B51, DRw52 are associated with steroid sensitivity. The attributive risk of steroid resistance is high for split A19+31+32, antigens B8, B55.

Treatment of Premenstrual Breakthrough of Depression With Adjunctive Oral Contraceptive Pills Compared With Placebo.

Two-thirds of women with depressive disorders report reemergence of depression premenstrually, or premenstrual exacerbation (PME), despite effective treatment of the underlying mood disorder during the remainder of the cycle. There is a paucity of studies that rigorously assess treatments targeting PME. Open-label data suggest that augmentation of antidepressants with the oral contraceptive pill (OCP) drospirenone and ethinyl estradiol (DRSP/EE) improves depressive symptoms that break through treatment premenstrually. We now report results of a randomized placebo-controlled OCP augmentation trial. Women with unipolar depressive disorders in remission on stable antidepressant doses with a 30% increase in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from the follicular to luteal phase were randomized to double-blind augmentation of antidepressant with either DRSP/EE or placebo for 2 months. The MADRS and Daily Record of Severity of Problems (DRSP) measures were anchored to the menstrual cycle phase. Of 32 women randomized, 25 (n = 12 DRSP/EE, n = 13 placebo) completed the trial. Premenstrual MADRS scores declined by a median of 43.6% and 38.9% (P = 0.59), and premenstrual DRSP scores declined by a median of 23.5% and 20.9% (P = 0.62) in the DRSP/EE and placebo groups, respectively. There was a trend toward greater improvement in premenstrual DRSP scores for women with fewer lifetime depressive episodes (r = -0.40, P = 0.06). Findings from this small randomized trial suggest that OCP augmentation of antidepressants may not be effective for treating premenstrual breakthrough of depression. Future studies should target women established to have hormonal sensitivity prior to antidepressant therapy and those with fewer lifetime depressive episodes.