Effects Of Ovarian Steroids Research Articles

FRI280 Partial Loss Of KNDy Neurons In Prenatally Androgen Treated Female Rats Alters The LH Secretion And Ovarian Morphology In A Model Of Polycystic Ovary Syndrome

Abstract Disclosure: N.S. Aquino: None. A. Campideli-Santana: None. L.M. Antunes: None. R. Araújo-Lopes: None. K.S. Silva: None. P.C. Henriques: None. D.D. Gusmão: None. M.P. Bernuci: None. R.E. Szawka: None. A.M. dos Reis: None. Polycystic Ovary Syndrome (PCOS) is a high-prevalent endocrine dysfunction, causing metabolic disorders and infertility. Women with PCOS show a disrupted hypothalamus-pituitary-gonadal (HPG) axis, which results in increased luteinizing hormone (LH) secretion, LH pulse frequency, and LH/follicle stimulating hormone (FSH) ratio. These changes are related to an impaired negative-feedback effect of ovarian steroids, estradiol and progesterone, on the gonadotrophin releasing-hormone (GnRH) neurons. Because the kisspeptin/neurokinin-B/dynorphin (KNDy) neurons of the arcuate (ARC) nucleus are responsible for mediating the ovarian steroid negative feedback, we investigated whether the ablation of KNDy neurons would change the LH secretion and ovarian morphology in a rat model of PCOS. Pregnant dams were treated with dihydrotestosterone (DHT, 3 mg/day; s.c) from days 16 to 19 of pregnancy. Three months after birth, the prenatally androgen-treated (PNA) offspring received intra-ARC stereotaxic injections of the neurokinin-3 receptor agonist conjugated with saporin (NK3-SAP) to induce the lesion of KNDy neurons and were submitted to serial blood sampling for LH measurement. PNA NK3-SAP rats had a moderate loss of ARC neurokinin-B-immunoreactive neurons (between 50-70%) compared with the Blank-SAP-injected PNA group. The PNA Blank-SAP rats displayed LH pulse frequency, pulse amplitude, and mean LH levels similar to control rats on diestrus. Remarkably, the partial loss of KNDy neurons increased the LH pulse amplitude and mean LH without changing the pulse frequency. Histological analysis was performed to investigate the outcome of the partial loss of KNDy neurons on the ovarian morphology in PNA rats. The numbers of primordial, primary, and secondary health follicles were decreased in PNA Blank-SAP compared with diestrus rats. Notably, the number of primordial follicles was partially restored in NK3-SAP rats. On the other hand, neither the number of atretic follicles nor the number of corpora lutea was changed in PNA Blank or NK3-SAP rats, indicating no change in the ovulatory function. Therefore, we provide evidence that KNDy neurons negatively modulate LH release and LH pulse amplitude in PNA rats. Moreover, the results suggest that KNDy neurons are involved in the reduction of the primordial follicle pool and ovarian reserve in PNA rats. Financial Support: Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Brazilian National Council for Scientific and Technological Development (CNPq), British Society for Neuroendocrinology (BSN). Presentation: Friday, June 16, 2023

The Divergent Effects of Ovarian Steroid Hormones in the MCF-7 Model for Luminal A Breast Cancer: Mechanistic Leads for Therapy.

The growth modulating effects of the ovarian steroid hormones 17β-estradiol (E2) and progesterone (PRG) on endocrine-responsive target tissues are well established. In hormone-receptor-positive breast cancer, E2 functions as a potent growth promoter, while the function of PRG is less defined. In the hormone-receptor-positive Luminal A and Luminal B molecular subtypes of clinical breast cancer, conventional endocrine therapy predominantly targets estrogen receptor function and estrogen biosynthesis and/or growth factor receptors. These therapeutic options are associated with systemic toxicity, acquired tumor resistance, and the emergence of drug-resistant cancer stem cells, facilitating the progression of therapy-resistant disease. The limitations of targeted endocrine therapy emphasize the identification of nontoxic testable alternatives. In the human breast, carcinoma-derived hormone-receptor-positive MCF-7 model treatment with E2 within the physiological concentration range of 1 nM to 20 nM induces progressive growth, upregulated cell cycle progression, and downregulated cellular apoptosis. In contrast, treatment with PRG at the equimolar concentration range exhibits dose-dependent growth inhibition, downregulated cell-cycle progression, and upregulated cellular apoptosis. Nontoxic nutritional herbs at their respective maximum cytostatic concentrations (IC90) effectively increase the E2 metabolite ratio in favor of the anti-proliferative metabolite. The long-term exposure to the selective estrogen-receptor modulator tamoxifen selects a drug-resistant phenotype, exhibiting increased expressions of stem cell markers. The present review discusses the published evidence relevant to hormone metabolism, growth modulation by hormone metabolites, drug-resistant stem cells, and growth-inhibitory efficacy of nutritional herbs. Collectively, this evidence provides proof of the concept for future research directions that are focused on novel therapeutic options for endocrine therapy-resistant breast cancer that may operate via E2- and/or PRG-mediated growth regulation.

Ovarian steroids modulate the systemic inflammatory response OF COWS challenged with lipopolysaccharide (LPS) intrauterine infusion

Postpartum uterine infections of dairy cows promote a local and systemic inflammation and interfere with reproductive efficiency. The aim of this study was to evaluate the effect of steroid hormones including progesterone (P4) and estradiol (E2) on the systemic inflammatory response of cows after being challenged with an intrauterine infusion of lipopolysaccharide (LPS). For this, a hemogram and serum dosage of haptoglobin (Hp) in eight primiparous Gir cows ovariectomized were performed on day (day 0) and after 24 h (day +1). Four cows (n = 4) were challenged (day 0) with 20 mL of 0.9% NaCl + 12.5 μg/kg LPS, and four cows (n = 4) were challenged (day 0) with 20 mL of 0.9% NaCl. For this, the study was divided in four experimental groups as: (1) Control group: without any hormonal treatment before day 0; (2) Group 24 h - E2: 1 mg of estradiol benzoate 24 h before (day −1); (3) Group 24 h - P4: 2.0 g of P4 device 24 h before (day −1); (4) Group 14 d - P4: 2.0 g of P4 device 14 days before (day −14). In the systemic response to LPS, there was an increase in Hp (control group; 24 h - P4 group; 14 d - P4 group), and on day +1 the Hp of 14 d - P4 group was higher when compared to the other groups. On day 0, the 14 d - P4 group had an increase in circulating leukocytes and lymphocytes cells than the control group (P < 0.01). On day +1 after LPS-challenge the 14 d - P4 group showed a decrease in circulating lymphocytes, eosinophils, and monocytes (P < 0.05). A neutrophilia with left shift in the two treatments with P4 (day +1), in addition to a thrombocytopenia and lower platelets compared to the 24 h - E2 group (P < 0.05) (day 0) were recorded. It was concluded that ovariectomized cows challenged with LPS, previously submitted to steroid hormones induce a systemic inflammatory response. Also, the systemic response is more intense after previous prolonged exposure to P4 and less intense after exposure to E2. This study provided important information relating the effect of ovarian steroids on the systemic inflammatory response of cows challenged with intrauterine LPS.

Subgenual cingulate resting regional cerebral blood flow in premenstrual dysphoric disorder: differential regulation by ovarian steroids and preliminary evidence for an association with expression of ESC/E(Z) complex genes

Substantial evidence suggests that circulating ovarian steroids modulate behavior differently in women with PMDD than in those without this condition. However, hormonal state-related abnormalities of neural functioning in PMDD remain to be better characterized. In addition, while altered neural function in PMDD likely co-exists with alterations in intrinsic cellular function, such a relationship has not been explored. Here, we investigated the effects of ovarian steroids on basal, resting regional cerebral blood flow (rCBF) in PMDD, and, in an exploratory analysis, we tested whether the rCBF findings were linked to the expression of ESC/E(Z) genes, which form an essential ovarian steroid-regulated gene-silencing complex. Resting rCBF was measured with oxygen-15 water PET (189 PET sessions in 43 healthy women and 20 women with PMDD) during three self-as-own-control conditions: GnRH agonist (Lupron)-induced ovarian suppression, estradiol add-back, and progesterone add-back. ESC/E(Z) gene expression data were obtained from RNA-sequencing of lymphoblastoid cell lines performed in a previous study and were examined in relation to hormone-induced changes in rCBF. In the rCBF PET data, there was a significant diagnosis-by-hormone interaction in the subgenual cingulate (PFDR = 0.05), an important neuroanatomical hub for regulating affective state. Whereas control women showed no hormonally-related changes in resting rCBF, those with PMDD showed decreased resting rCBF during both estradiol (P = 0.02) and progesterone (P = 0.0002) add-back conditions. In addition, in PMDD, ESC/E(Z) gene expression correlated with the change in resting rCBF between Lupron-alone and progesterone conditions (Pearson r = −0.807, P = 0.016). This work offers a formulation of PMDD that integrates behavioral, neural circuit, and cellular mechanisms, and may provide new targets for future therapeutic interventions.

Cell Specific Expression of Vascular Endothelial Growth Factor Receptor-2 (Flk-1/KDR) in Developing Mice Embryo and Supporting Maternal Uterine Tissue during Early Gestation (D4-D7).

BackgroundVascular endothelial growth factor (VEGF) and the corresponding receptors play key role in vascu- logenesis and angiogenesis processes. VEGF is one of the prime candidates in regulating embryo implantation by increasing vascular permeability. VEGF receptor-2, also called Flk-1/KDR, is one of the prime receptor which is actively involved in the execution of various functions of VEGF. However, precise role of this receptor during early gestation period is yet to be addressed. In the present study, expression of Flk-1/KDR during peri-implantation mice uterus as well as fetal-maternal tissues from day 4-day 7 (D4-D7) of gestation was investigated.Materials and MethodsIn this experimental study, localization of Flk-1/KDR was investigated by immunohisto- chemistry and immunofluorescence techniques, in paraffin embedded tissue sections. Flk-1/KDR protein and mRNA expressions were investigated by western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively. Effects of ovarian steroids on expression of Flk-1/KDR were also assessed by estrogen and progesterone antagonist treatment.ResultsUterine tissue on D4 showed strong expression of Flk-1/KDR in luminal and uterine glandular epithelium. On D5 and D6, differential expression of Flk-1/KDR was evidenced in certain cell types of the embryo, maternal tissues and fetal-maternal interface with varied intensity. Flk-1/KDR was specifically expressed in the ectoplacental cone (EPC) and various cells of the embryo on D7. Flk-1/KDR expression was not evidenced in the estradiol-17β (E2) and progesterone (P4) antagonist treated uterus. Western blotting result revealed presence of Flk-1/KDR protein in the all gestation days, except antagonist treated uterus. qRT-PCR analysis showed significant increase of Flk-1/KDR mRNA transcript on D6 and D7.ConclusionSpatial-temporal expression of Flk-1/KDR during peri-implntation period in mice uterus especially in the feto-maternal interface was observed. This spatio-temporal specificity as well as increased expression of Flk-1/KDR could be one of the determinants for establishment of fetal-maternal cross talk during the critical period of develop- ment.

Steroid regulation of secreted phosphoprotein 1 (SPP1) expression in ovine endometrium.

Secreted phosphoprotein 1 (SPP1) is an extracellular matrix glycoprotein that is highly expressed at the maternal-fetal interface and is a critical mediator of embryo implantation. The objectives of this study were to examine the spatial and temporal cyclical expression patterns and steroid regulation of SPP1 mRNA and protein in ovine endometrium, which may be further indicative of their functionality in embryo implantation. Uterine tissue was obtained following hysterectomy from ovariectomised ewes treated with ovarian steroids. In parallel, invitro culture of endometrial cells was used to investigate the effects of ovarian steroids on SPP1 expression in endometrial and luminal epithelial (LE) cells. A significant sustained mid-luteal phase increase in SPP1 mRNA in intercaruncular regions of the endometrium was observed, indicating that glandular epithelium is likely to be the primary source of SPP1 production. This increase in SPP1 was induced by progesterone treatment and was shown at the protein level by immunohistochemistry analysis. Similarly, treatment of stromal cells with 10ng mL-1 progesterone or in combination with 1ng mL-1 oestradiol significantly increased SPP1 expression (P<0.05). Collectively, expression levels of SPP1 are cycle-dependent and peak in the progesterone-dominant luteal phase. They are dependent on the interaction of uterine LE and stromal cells and may involve paracrine signalling by progesterone receptor-positive stromal cells.

Effect of ovarian steroids on vascular endothelial growth factor a expression in bovine uterine endothelial cells during adenomyosis

BackgroundAdenomyosis is a uterine dysfunction defined as the presence of endometrial glands within the myometrium. There is evidence that proangiogenic factors may play a role during the development of adenomyosis; however, exact mechanism remains unknown. The aim of the study was to determine the action of vascular endothelial growth factor A (VEGFA) in uterine tissue and uterine vascular endothelial cells during adenomyosis.ResultsUterine tissues were collected and examined for the presence and extent of adenomyosis. Gene and protein expression of VEGFA and its two receptors (VEGFR1 and VEGFR2) was evaluated with quantitative polymerase chain reaction and Western blotting, respectively, in endometrium and myometrium during adenomyosis. Immunolocalization of VEGFA and its receptors within uterine tissues during adenomyosis was also determined. In an in vitro experiment, endothelial cells from non-adenomyotic bovine uteri were treated with media conditioned by non-adenomyotic or adenomyotic uterine slices treated with 17-beta-oestradiol (E2) or progesterone (P4). Both gene and protein expression of VEGFR2 were elevated in endometrium in stages 3–4 of adenomyosis. Protein expression of VEGFA and VEGFR2 as well as VEGFA secretion were increased in endothelial cells treated with media conditioned by adenomyotic uterine slices after E2 treatment.ConclusionsResults suggest that VEGFA signalling is an important component, next to E2, that enhances VEGFA action and participates in adenomyosis development in cows.

C-type natriuretic peptide: a link between hyperandrogenism and anovulation in a mouse model of polycystic ovary syndrome.

The polycystic ovary (PCO) syndrome (PCOS) is the most common cause of anovulatory infertility in women and is associated with several clinical disorders. Despite the great amount of research in the area, mechanisms involved in the genesis of this syndrome remain poorly understood. In a recent issue of Clinical Science (vol. 132, issue 7, 759-776), Wang and colleagues, highlight the important role of overactivated C-type natriuretic peptide (CNP) and natriuretic peptide receptor 2 (CNP/NPR2) system in preventing oocyte maturation and ovulation in PCOS mice model induced by androgen. Dehydroepiandrosterone (DHEA) treatment caused anovulation, high levels of androgen and estrogen receptors (AR and ER) in the ovary, high expression of CNP and natriuretic peptide receptor 2 (NPR2) in granulosa cells (GC), and an increase in testosterone and estradiol (E2) levels in sera. The high level of CNP/NPR2 was associated with oocyte meiotic arrest and very low ovulation rate. Treatment with human chorionic gonadotropin (hCG) or inhibitors of AR or ER reduced the level of CNP/NPR2, which resulted in meiotic resumption and ovulation. The article provided important information for understanding the effect of ovarian steroids on control of oocyte maturation and fertility and highlighted CNP/NPR2 as a specific pathway that is potentially involved in the ovulatory disruption in PCOS.

Effects of Sex Steroids on the Spinal Gastrin-Releasing Peptide System Controlling Male Sexual Function in Rats.

The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord controls male sexual function in rats. In contrast, in female rats, GRP neurons could scarcely be detected around puberty when circulating ovarian steroid hormones such as estradiol and progesterone levels are increasing. However, little information is available on feminizing or demasculinizing effects of ovarian steroids on the central nervous system in female puberty and adulthood. In this study, to visualize the spinal GRP neurons in vivo, we generated a GRP-promoter-Venus transgenic (Tg) rat line and studied the effects of the sex steroid hormones on GRP expression in the rat lumbar cord by examining the Venus fluorescence. In these Tg rats, the sexually dimorphic spinal GRP neurons controlling male sexual function were clearly labeled with Venus fluorescence. As expected, Venus fluorescence in the male lumbar cord was markedly decreased after castration and restored by chronic androgen replacement. Furthermore, androgen-induced Venus expression in the spinal cord of adult Tg males was significantly attenuated by chronic treatment with progesterone but not with estradiol. A luciferase assay using a human GRP-promoter construct showed that androgens enhance the spinal GRP system, and more strikingly, that progesterone acts to inhibit the GRP system via an androgen receptor-mediated mechanism. These results demonstrate that circulating androgens may play an important role in the spinal GRP system controlling male sexual function not only in rats but also in humans and that progesterone could be an important feminizing factor in the spinal GRP system in females during pubertal development.

Interactive effects of ovarian steroid hormones on alcohol use and binge drinking across the menstrual cycle.

Patterns and features of substance use and abuse vary across the menstrual cycle in humans. Yet, little work has systematically examined the within-person relationships between ovarian hormone changes and alcohol use across the menstrual cycle. Our study was the first to examine the roles of within-person levels of estradiol (E2) and progesterone (P4) in relation to daily alcohol use and binge drinking in young women. Participants were 22 naturally cycling women, ages 18-22, recruited through a university subject pool who reported any alcohol use and who completed a screening visit assessing study eligibility, followed by 35 subsequent days of data collection. E2 and P4 were obtained via enzyme immunoassay of saliva samples collected by participants each morning, 30 min after waking. Presence and degree of daily substance use were obtained using an adaptation of the Timeline FollowBack Interview completed daily. Results indicated that elevated E2 in the context of decreased P4 levels were associated with higher risk of drinking and binge drinking. These effects were present only on weekend days. Results are suggestive of a dual risk model in which both ovulatory E2 increases and perimenstrual P4 decreases increase risk for drinking. Differential associations of steroids with drinking across the menstrual cycle may suggest the need for clinical assessment of substance use to take into account hormone dynamics and menstrual cycle phase. (PsycINFO Database Record

Brain-derived neurotrophic factor Val66Met genotype and ovarian steroids interactively modulate working memory-related hippocampal function in women: a multimodal neuroimaging study.

Preclinical evidence suggests that the actions of ovarian steroid hormones and brain-derived neurotrophic factor (BDNF) are highly convergent on brain function. Studies in humanized mice document an interaction between estrus cycle-related changes in estradiol secretion and BDNF Val66Met genotype on measures of hippocampal function and anxiety-like behavior. We believe our multimodal imaging data provide the first demonstration in women that the effects of the BDNF Val/Met polymorphism on hippocampal function are selectively modulated by estradiol. In a 6-month pharmacological hormone manipulation protocol, healthy, regularly menstruating, asymptomatic women completed positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) scans while performing the n-back working memory task during three hormone conditions: ovarian suppression induced by the gonadotropin-releasing hormone agonist, leuprolide acetate; leuprolide plus estradiol; and leuprolide plus progesterone. For each of the three hormone conditions, a discovery data set was obtained with oxygen-15 water regional cerebral blood flow PET in 39 healthy women genotyped for BDNF Val66Met, and a confirmatory data set was obtained with fMRI in 27 women. Our results, in close agreement across the two imaging platforms, demonstrate an ovarian hormone-by-BDNF interaction on working memory-related hippocampal function (PET: F2,37=9.11, P=0.00026 uncorrected, P=0.05, familywise error corrected with small volume correction; fMRI: F2,25=5.43, P=0.01, uncorrected) that reflects differential hippocampal recruitment in Met carriers but only in the presence of estradiol. These findings have clinical relevance for understanding the neurobiological basis of individual differences in the cognitive and behavioral effects of ovarian steroids in women, and may provide a neurogenetic framework for understanding neuropsychiatric disorders related to reproductive hormones as well as illnesses with sex differences in disease expression and course.

Effects of Ovarian Steroids on Osteoblast Viability and Mineralization

Effects of Ovarian Steroids on Osteoblast Viability and Mineralization

OS 11-04 Impact of gonadectomy on sympatho-vagal balance in male and female normotensive rat

OBJECTIVE: It is well established that autonomic nervous system and sympatho-vagal balance plays an important role in maintaining arterial blood pressure (ABP) (Salman IM., 2016) and that autonomic regulation of ABP differs between males and females (Hart EC et al., 2014). We hypothesised that sex hormones affect blood pressure via the autonomic nervous system and that the late development of hypertension in females is due to protective effects of ovarian steroids in females rather than due to detrimental effects of testosterone in males. DESIGN AND METHOD: We used adult, 12 months old, Wistar female and male, intact and gonadectomised rats (n = 8, per each group). Resting ABP was recorded by radio-telemetry. Heart rate (HR) and ABP variability were calculated using Spike2 software. Effect of gender and gonadectomy were assessed by two-way Anova. RESULTS: Females had lower systolic (S)BP compared to males (121 ± 1 vs 128 ± 2 mmHg; P < 0.05). Intact (81 ± 2 mmHg) but not ovariectomised (89 ± 2 mmHg) females had lower diastolic (D)BP compared to males (91 ± 1 mmHg; P < 0.01). Moreover, intact (353 ± 6bpm) but not ovariectomised (307 ± 5 bpm) females had higher HR compared to males (353 ± 6bpm; P < 0.001). However, ovariectomy did not influence the higher respiratory rate in females vs males (91 ± 3 vs 78 ± 3 bpm; P < 0.001).Power spectra analysis of SBP shows that males (22.4 ± 3) and ovariectomised females (26.9 ± 3) had lower High Frequency percentage vs females (38 ± 3; P < 0.05) suggesting that female hormones affect ABP by modulating the parasympathetic activity. The Very Low Frequency percentage was higher in males vs females (40 ± 4 vs 28 ± 4; P < 0.05) suggesting that sympathetic vasomotor tone might play an important role in the differential regulation of SBP between males and females. CONCLUSIONS: Altogether, this results show that female hormones have a positive effect on ABP and that they affect ABP via modulating parasympathetic activity. Further analyses of BP and HR variability at different ages are needed to determine the interaction between age, BP and gender.

Progesterone-induced amplification and advancement of GnRH/LH surges are associated with changes in kisspeptin system in preoptic area of estradiol-primed female rats

The time course effects of ovarian steroids on kisspeptin and GnRH/LH systems is not totally clarified. We investigated the temporal relationship among kisspeptin and GnRH mRNA and kisspeptin content in the preoptic area (POA), GnRH content and release in the medial basal hypothalamus (MBH) and plasma LH levels under different steroid treatments. Ovariectomized rats treated with oil (OVOO), oil plus single dose of estradiol (OVOE), oil plus single dose of progesterone (OVOP), estradiol for 3 days plus oil (OVEO) or estradiol for 3 days plus progesterone (OVEP) were hourly decapitated from 10:00 to 17:00 or had the MBH microdialyzed from 09:00 to 19:00. Estradiol and progesterone acutely increased POA kisspeptin content without altering POA kisspeptin mRNA levels. Short-term exposure to both hormones stimulated MBH GnRH content, although no GnRH/LH surges had occurred. Chronic estradiol-treatment increased both kisspeptin mRNA levels and content in the POA, demonstrating that long exposure to estradiol is required to activate the whole kisspeptin synthesis machinery. This was followed by the peak in the GnRH/LH release. In estradiol-primed rats, progesterone further increased POA kisspeptin content, amplified and advanced GnRH/LH surges, with no additional change on POA kisspeptin mRNA. The data show an estradiol-induced temporal association between kisspeptin increase in the POA and GnRH/LH surges. Interestingly, the classic action of progesterone in amplifying and accelerating the GnRH/LH surges seems to occur by a mechanism which involves POA kisspeptin system.

Pathways regulating the nonhuman primate cervix

Mucus secretion plays a crucial role in the passage of sperm through the primate cervix. Estrogens and progestins affect cervical mucus secretion and quality (1,2), but the molecular pathways mediating the effects of ovarian steroids on the cervix are poorly understood. Macaques are excellent primate animal models for studies that involve invasive procedures. The aim of this study was to identify hormonally regulated genes and their related biological pathways in the macaque cervix during the menstrual cycle.

English

A wide spectrum of biological function is regulated by the cyclic changes in estrogen and progesterone levels during regular menstrual cycle. However limited literature is available concerning the relationship of these hormones and cardiac autonomic activity. In the present study, we hypothesize that there would be heart rate variability during different phases of menstrual cycle, which can be attributed to the effect of ovarian steroids on cardiovascular function in women. The aim of the study is to compare the cardiac autonomic activity in the different phases of menstrual cycle (Menstrual, follicular and luteal phases) using heart rate variability. The objective is to establish a physiological correlation between the cardiac autonomic activity and different phases of menstrual cycle. The study was conducted in 48 regularly menstruating young female, of age group 18-30yrs, in the Upgraded Department of Physiology, Osmania medical college, from December 2011 to August 2013, using LABCHART software provided by ADLABS. The power spectral analysis of HRV was used to calculate low frequency(LF), high frequency (HF) component and their ratio (LF/HF) during menstrual (2±1 days), follicular(11±1 day) and luteal phases (20±1day) from the first day of bleeding. Results showed a significant increase was noted in low frequency component in luteal phase compared to follicular phase (p=0.000), whereas, a tendency for increase in high frequency component was observed in follicular phase (p=0.004). Furthermore, LF/HF was significantly higher in luteal phase than in the follicular phase (p=0.000) indicating an increased sympathetic activity. The conclusion is regulation of autonomic tone is modified during menstrual cycle. The alteration in the Ovarian hormones alterations along the menstrual cycle are associated with corresponding significant changes in multiple neuro-humoral homeostatic mechanisms regulating the cardio- vascular system. 4 The general presence of functional sex steroid hormone receptors in the cardiovascular system is well established and their expression in both heart and blood vessels have been recognized for decades.5,6,7,8 Estrogen is also associated with lower levels of endothelin and decreased sensitivity to the vaso-constrictive effects of peptide. The presence of estrogen receptors in the heart, vascular smooth muscle and autonomic brain centers, suggest a possible involvement in the regulation of cardiovascular system. In the follicular phase, estrogen causes an up-regulation in the cardiovascular or myometrial adreno-receptor.

Suppressive effects of ovarian steroid hormones on the expression of synaptonemal complex protein 1 in organ-cultured testis of neonatal mice

Suppressive effects of ovarian steroid hormones on the expression of synaptonemal complex protein 1 in organ-cultured testis of neonatal mice

Do Hormones Influence Women's Sex? Sexual Activity over the Menstrual Cycle

In mammals, the effects of ovarian steroids influence sexual behavior. In humans, there are a few studies that take into account if ovulation occurs. The study aims to investigate if a woman's sexuality changes during the week and over the menstrual cycle, and if so, in what way. This is a prospective cohort study; 1,957 heterosexual women were involved over the period January 2004-December 2011. Two subgroups were taken into consideration, women having a partner and singles. Sexual interview and the Female Sexual Function Index and Female Sexual Distress Scale questionnaires were used to exclude women with sexual dysfunction. Women with ovulation confirmed by sonography were enrolled. Women were given diary cards on which to report their daily sexual activity. Serum concentrations of estradiol, progesterone, total testosterone, sex hormone binding globulin, and free androgen index were measured during the follicular, periovular, and luteal phase of the menstrual cycle. One thousand one hundred eighty women (age range 18-40 years) were included in the analyses. Of them, 925 had a heterosexual relationship and 255 were single. Women with a partner had more sexual activity during the weekend, while the singles had a constant sexual activity over the week. The sexual activity of singles was higher during the ovulatory phase and lower during menses than that of the women with a partner. A linear correlation between sexual activity and androgenic hormonal profile during the menstrual cycle in women with and without a partner was observed. Ovarian steroids modulate a woman's sexual activity. This aspect was more evident in singles than in women having a partner, in which a variety of nonhormonal factors can have a role.

Prenatal Alcohol Exposure Results in Long-Term Serotonin Neuron Deficits in Female Rats: Modulatory Role of Ovarian Steroids

Previous studies on male rodents found that prenatal alcohol exposure (PAE) decreases the number of serotonin immunoreactive (5-HT-ir) neurons in the brainstem. However, data on the effects of PAE in females are lacking. In light of known sex differences in responsiveness of the 5-HT system and known effects of estrogen (E2 ) and progesterone (P4 ) in the brain, we hypothesized that sex steroids will modulate the adverse effects of PAE on 5-HT neurons in adult females. Adult females from 3 prenatal groups (Prenatal alcohol-exposed [PAE], Pair-fed [PF], and ad libitum-fed Controls [C]) were ovariectomized (OVX), with or without hormone replacement, or underwent Sham OVX. 5-HT-ir cells were examined in key brainstem areas. Our data support the hypothesis that PAE has long-term effects on the 5-HT system of females and that ovarian steroids have a modulatory role in these effects. Intact (Sham OVX) PAE females had marginally lower numbers of 5-HT-ir neurons in the dorsal raphe nucleus of the brainstem compared with PF and C females. This marginal difference became significant following removal of hormones by OVX. Replacement with E2 restored the number of 5-HT-ir neurons in PAE females to control levels, while P4 reversed the effects of E2 . Importantly, despite these differential responses of the 5-HT system to ovarian steroids, there were no differences in E2 and P4 levels among prenatal treatment groups. These data demonstrate long-term, adverse effects of PAE on the 5-HT system of females, as well as differential sensitivity of PAE compared with control females to the modulatory effects of ovarian steroids on 5-HT neurons. Our findings have important implications for understanding sex differences in 5-HT dysfunction in depression/anxiety disorders and the higher rates of these mental health problems in individuals with fetal alcohol spectrum disorder.

Duodenumda Ovaryum Steroidlerinin Etkisinde Nitrik Oksidin Rolü

Summary The purpose of this study is to determine the distribution and expression of nNOS, eNOS and iNOS and to evaluate the role of ovarian steroids in NOS expressions in the duodenum tissues of rats. Rats in the control group (Ov group) were injected intramuscularly with sesame oil for 10 days, whereas rats in the first, second, and third experimental groups received intramuscular administration of progesterone (P group), 17β-estradiol (E2 group) and 17beta-estradiol and progesterone (E2 + P group), respectively. According to the results of an immunohistochemical evaluation, a severe nNOS expression was observed in both the crypts and nerve fibers of the duodenum in the Ov, P and E2 groups but decreased in the E2 + P group. It was determined that iNOS expression increased in the surface epithelial cells and crypts of P group while it only decreased in crypts of E2 group. There was severe eNOS expression in crypts in all treatment groups, while it only increased in the surface epithelial cells in the E2 group. The results of the current experiment suggest that the effect of ovarian steroids on duodenum absorbtion and microvascular protection can be mediated by crypt and epithelial nNOS, iNOS and eNOS expressions in rats. Besides the estradiol and progesterone administration together inhibit nNOS activitiy in the duodenum.