The 17α and 17β Isomers of Estradiol Both Induce Rapid Spine Synapse Formation in the CA1 Hippocampal Subfield of Ovariectomized Female Rats

Previous studies have demonstrated that estradiol-17β and estradiol-17α both induce short-latency effects on spatial memory in rats, estradiol-17α being at least as potent as its 17β isomer. To determine whether the mechanisms underlying these behavioral responses might include effects on hippocampal synaptic plasticity, CA1 pyramidal spine synapse density (PSSD) was measured in ovariectomized rats within the first few hours after sc estrogen injection. PSSD increased markedly (by 24%) 4.5 h after the administration of 45 μg/kg estradiol-17β. The PSSD response was significantly greater (44% above control) 30 min after estradiol-17β injection and was markedly dose dependent; a 3-fold lower estradiol-17β dose (15 μg/kg) did not significantly affect CA1 PSSD at either 30 min or 4.5 h. Estradiol-17α was a more potent inducer of PSSD than estradiol-17β. Dose-response analysis determined an ED50 for the effect of estradiol-17α on PSSD of 8.92 ± 1.99 μg/kg, with a maximal response at 15 μg/kg. These results demonstrate that high doses of estradiol induce rapid changes in CA1 PSSD. CA1 spine synapse formation appears to be more sensitive to estradiol-17α than to estradiol-17β, paralleling previous data on the effects of these two steroids on spatial memory. Rapid remodeling of hippocampal synaptic connections may thus contribute to the enhancement of spatial mnemonic processing observed within the first few hours after estrogen treatment. The potency of estradiol-17α suggests that hormone replacement therapy using this steroid might be useful clinically in ameliorating the impact of low endogenous estrogen production on the development and progression of neurodegenerative disorders involving the hippocampus.

Download Full-text

Effects of ovariectomy, estrogen and soy isoflavones in rats submandibular glands

Brazilian Dental Science ◽

10.14295/bds.2017.v20i3.1443 ◽

2017 ◽

Vol 20 (3) ◽

Author(s):

Luana Marotta Reis Vasconcellos ◽

Vanessa Ávila Sarmento Silveira ◽

Raphaela Silveira Medeiros ◽

Márian Yaktin Amorin ◽

Yasmin Rodarte Carvalho ◽

...

Keyword(s):

Estrogen Receptor ◽

Salivary Glands ◽

Hormone Replacement ◽

Soy Isoflavones ◽

Estrogen Receptor Β ◽

Female Rats ◽

Ovariectomized Rats ◽

Nuclear Antigen ◽

Soy Isoflavone ◽

Submandibular Glands

Objective: A decrease in granular convoluted tubule (GCT) cells and acini occurs in the submandibular glands of castrated female rats, while in rats submitted to hormone replacement and phytotherapy with soy isoflavones, this effect is reversed. This study aimed to elucidate the mechanisms through which these changes occur. Material and Methods: Rats (n=84) were ovariectomized and 21 were sham-operated. Ovariectomized rats were randomly subdivided and orally administered the following: 17 β-estradiol (OVX-E; n=21), 15 mg/kg/day of soy isoflavone extract (OVX-I; n=21), 17 β-estradiol + soy isoflavone extract (OVX-A; n=21); and water as placebo (OVX; n=21). The rats were euthanized three, five and eight weeks after ovariectomy. The submandibular salivary glands were submitted to histological processing with HE stain and immunohistochemistry was performed using the streptavidin-biotin-peroxidase complex. The cell area and the expression of proliferating cell nuclear antigen and estrogen receptor β were evaluated. Results: The results were statistically analyzed by ANOVA and Tukey test. A decrease in the area of GCT cells in the OVX, was observed, in contrast with an increase in the OVX-E. PCNA in the acinar cells and estrogen receptors were elevated in the OVX-I group. Conclusion: Castration exerts an immediate reductive effect on the volume of GCT cells. Estrogens, soy isoflavones and their combination have different mechanisms of action on the homeostasis of the gland. Estrogens cause an increase in GCT cells area, while isoflavones enhance cell proliferation and the expression of estrogen receptor-β. Their association showed no additional increase in the effect studied.KeywordsEstrogen; Morphometry; Salivary glands; Soy isoflavones.

Download Full-text

THE INVESTIGATION OF PHARMACOLOGICAL PROPERTIES OF VAGINAL GEL WITH RESVERATROL AND HYALURONIC ACID IN CONDITIONS OF EXPERIMENTAL HYPOESTROGENIC STATE IN RATS

Medical Science of Ukraine (MSU) ◽

10.32345/2664-4738.1.2021.10 ◽

2021 ◽

Vol 17 (1) ◽

pp. 74-82

Author(s):

O.A. Stryha ◽

G.V. Zaychenko ◽

S.I. Savosko ◽

K.Y. Sorokopud

Keyword(s):

Hyaluronic Acid ◽

Sex Hormones ◽

Hormone Replacement ◽

Female Rats ◽

Ovariectomized Rats ◽

Blood Levels ◽

Vaginal Mucosa ◽

Pharmacological Properties ◽

Vaginal Gel ◽

Vaginal Secretions

Relevance. The menopausal period due to irreversible loss of ovarian function is accompanied by various clinical symptoms and systemic changes. In turn, hormone replacement therapy has a number of contraindications and side effects, so now there is a need to find and create prophylactic and therapeutic agents based on natural compounds that are related to β-estrogen receptors. Vaginal gel with resveratrol and hyaluronic acid can reduce atrophic manifestations of the vaginal mucosa and affect various symptoms of menopause. However, the nature of the effect, dosage, and consequences of long-term use of resveratrol need further study. Objective: to study pharmacological properties of a new vaginal gel with resveratrol and hyaluronic acid (HA) in a model of hypoestrogenism in ovariectomized rats. Materials and methods. The experiments were performed on 24 outbred white nonlinear female rats, which were divided into 4 groups: intact control, controlled pathology, controlled pathology, and administration of resveratrol with hyaluronic acid, controlled pathology, and administration of a comparison drug with synthetic estrogen. The effectiveness of the drugs was assessed by their effect on the blood levels of the sex hormones estrogen and progesterone, on body weight, on body temperature, on the pH of vaginal secretions, on the state of the vaginal mucosa. Results. 28-day vaginal injection of gel with resveratrol and hyaluronic acid slowed down and normalized weight gain of ovariectomized female rats, stabilized skin temperature and induced normalization of the pH of vaginal secretions of the vagina, normalized the level of sex hormones in the blood, promoted the restoration of the epithelial plate of the vagina. Conclusions. The results showed the feasibility of developing and using a new vaginal gel with resveratrol as an alternative to hormone-containing drugs for the prevention or treatment of pathological hypoestrogenic conditions arising from estrogen deficiency.

Download Full-text

Effect of Lepidium meyenii (maca) on spatial memory and brain oxidative damage of ovariectomized-rats exposed to mobile phone

Revista Vitae ◽

10.17533/udea.vitae.v28n1a342472 ◽

2021 ◽

Vol 28 (01) ◽

Author(s):

Carmen Marín-Tello ◽

Haydée Villafana-Medina ◽

José Aliaga-Arauco ◽

Violeta Malpartida-Tello ◽

Elio Castañeda-Marín ◽

...

Keyword(s):

Oxidative Stress ◽

Oxidative Damage ◽

Spatial Memory ◽

Mobile Phone ◽

Female Rats ◽

Ovariectomized Rats ◽

High Concentration ◽

Lepidium Meyenii ◽

Mobile Phone Radiation ◽

Positive Effect

Background: Oxidative stress, genetic expression changes, and decomposition of the blood-brain barrier have been shown to be caused by exposure to radiofrequency radiation (RFR); therefore, the search for drugs or food products that offer some protection from these effects has attracted interest. Lepidium meyenii (maca) is a native Andean plant known for its effects on the female reproductive system as well as its immunomodulating, energizing, antioxidant, and nutritive properties due to its high concentration of alkaloids, amino acids, glucosinolates, fatty acids, and macamides. Objectives: We aim to determine the effect of dietary maca supplementation on spatial memory and cerebral oxidative damage in rats with induced menopause and/or with exposure to mobile phone radiation. Method: Female rats divided into 6 groups (six rats in each group): control or not ovariectomized (O-), ovariectomized (O+), ovariectomized + estrogen (O+E+), ovariectomized + estrogen + irradiated (O+E+I+), ovariectomized + maca (O+M+), and ovariectomized + maca + irradiated (O+M+I). Rat spatial memory was tested using the Morris water navigation task. Rats were sacrificed, and cerebral malondialdehyde was measured. Results: After exposure to mobile phone radiation, the group supplemented with maca showed improved spatial memory and lower levels of malondialdehyde than the estrogenized group. Conclusions: Our results suggest that consumption of maca has a positive effect on the maintenance of memory and decreases oxidative stress caused by mobile phone radiation. However, it is necessary to extend this work using a larger sample size.

Download Full-text

Estrogen deficiency and periodontal condition in rats: a radiographic and macroscopic study

Brazilian Dental Journal ◽

10.1590/s0103-64402006000300005 ◽

2006 ◽

Vol 17 (3) ◽

pp. 201-207 ◽

Cited By ~ 17

Author(s):

Ana Lia Anbinder ◽

Marcela de Almeida Prado ◽

Marianne Spalding ◽

Ivan Balducci ◽

Yasmin Rodarte Carvalho ◽

...

Keyword(s):

Risk Factor ◽

Bone Loss ◽

Periodontal Disease ◽

Alveolar Bone ◽

Alveolar Bone Loss ◽

Estrogen Deficiency ◽

Female Rats ◽

Ovariectomized Rats ◽

Furcation Involvement ◽

The Impact

The purpose of this study was to evaluate the impact of ovariectomy-induced estrogen deficiency as a risk factor of periodontal disease in rats. Forty 90-day old female rats were either ovariectomized (OVX; n=20) or sham operated (SHAM; n=20). After 30 days, periodontitis was induced by placement of a cotton ligature around the upper second molars of 10 OVX and 10 SHAM animals. All animals were sacrificed 5 weeks later. Body weight was assessed before all surgical procedures. The left hemimaxillas were removed and the percentage of periodontal bone support was determined radiographically and buccal alveolar bone loss was determined macroscopically using an image-analysis software. Furcation involvement was also evaluated. Data were analyzed statistically by ANOVA at 5% significance level. Within the evaluated period, the ovariectomized rats gained more weight than the sham-operated animals (p<0.001). The animals in which periodontitis was induced had less bone support, greater alveolar bone loss and furcation involvement than those without ligature (p<0.001). However, there was no difference between ovariectomized and sham-operated animals (p>0.05). Based on the findings of this study, estrogen deficiency could not be considered as a risk factor for periodontal disease.

Download Full-text

Paraventricular Dynorphin A Neurons Mediate LH Pulse Suppression Induced by Hindbrain Glucoprivation in Female Rats

Endocrinology ◽

10.1210/endocr/bqaa161 ◽

2020 ◽

Vol 161 (11) ◽

Author(s):

Hitomi Tsuchida ◽

Parvin Mostari ◽

Koki Yamada ◽

Sae Miyazaki ◽

Yuki Enomoto ◽

...

Keyword(s):

Receptor Gene ◽

Critical Role ◽

Female Rats ◽

Ovariectomized Rats ◽

Central Administration ◽

Dynorphin A ◽

Gonadotropin Secretion ◽

Feedback Level ◽

Estradiol 17Β

Abstract Malnutrition suppresses reproductive functions in mammals, which is considered to be mostly due to the inhibition of pulsatile gonadotropin-releasing hormone (GnRH)/gonadotropin secretion. Accumulating evidence suggests that kisspeptin neurons in the arcuate nucleus (ARC) play a critical role in the regulation of pulsatile GnRH/gonadotropin release. The present study aimed to examine if the hypothalamic dynorphin A (Dyn) neurons mediate the suppression of GnRH/luteinizing hormone (LH) pulses during malnutrition. Ovariectomized rats treated with a negative feedback level of estradiol-17β-treated (OVX+E2) were administered with intravenous (iv) or fourth cerebroventricle (4V) 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, to serve as a malnutrition model. Central administration of a Dyn receptor antagonist blocked the iv- or 4V-2DG-induced suppression of LH pulses in OVX+E2 rats. The 4V 2DG administration significantly increased the number of Pdyn (Dyn gene)-positive cells co-expressing fos in the paraventricular nucleus (PVN), but not in the ARC and supraoptic nucleus (SON), and the iv 2DG treatment significantly increased the number of fos and Pdyn-co-expressing cells in the PVN and SON, but decreased it in the ARC. The E2 treatment significantly increased Pdyn expression in the PVN, but not in the ARC and SON. Double in situ hybridization for Kiss1 (kisspeptin gene) and Oprk1 (Dyn receptor gene) revealed that around 60% of ARC Kiss1-expressing cells co-expressed Oprk1. These results suggest that the PVN Dyn neurons, at least in part, mediate LH pulse suppression induced by the hindbrain or peripheral glucoprivation, and Dyn neurons may directly suppress the ARC kisspeptin neurons in female rats.

Download Full-text

Interleukin-1β fever in rats: gender difference and estrous cycle influence

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.275.5.r1450 ◽

1998 ◽

Vol 275 (5) ◽

pp. R1450-R1454 ◽

Cited By ~ 9

Author(s):

A. Mouihate ◽

X. Chen ◽

Q. J. Pittman

Keyword(s):

Estrous Cycle ◽

Gonadal Hormones ◽

Female Rats ◽

Ovariectomized Rats ◽

Febrile Response ◽

Immune System Activation ◽

System Activation ◽

Fever Response ◽

Estradiol 17Β ◽

Hormonal Levels

Evidence exists to support the concept of sex difference in immune system activation by pyrogenic cytokines. In this study, fever development was monitored to analyze the effect of peripheral administration of interleukin (IL)-1β (1 μg/kg) in adult male and cycling or ovariectomized female rats with or without ovarian hormonal replacement. In male and randomly cycling female rats, a similar increase in body temperature occurred after intraperitoneal IL-1β injection. Two representative stages of estrus with higher and lower levels of ovarian hormones (proestrus and diestrus, respectively) were chosen for study of the febrile response induced by IL-1β. The fever induced by IL-1β was found to be significantly higher and more prolonged in females at proestrus than at diestrus. The differential fever response seems to be mainly linked to the ovarian hormonal levels because bilaterally ovariectomized females, supplemented with sequential injections of estradiol 17β and progesterone, showed a significantly higher IL-1β fever than did ovariectomized rats receiving estradiol 17β only. These results indicate that gonadal hormones can influence fever development and raise the possibility of interaction between sex hormones and thermogenesis in females during the estrous cycle.

Download Full-text

Protective effect of swimming and genistein on the expression of microRNA 132, insulin growth factor 1, and brain-derived neurotrophic factor genes, as well as spatial memory, in the hippocampus of diabetic ovariectomized rats

10.32592/ajnpp.2021.8.4.102 ◽

2021 ◽

pp. 178-185

Keyword(s):

Growth Factor ◽

Spatial Memory ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Diabetic Rats ◽

Female Rats ◽

Ovariectomized Rats ◽

Bdnf Expression ◽

Insulin Growth Factor ◽

Combined Use

Background and Objective: The present study aimed to assess the effects of the combined use of exercise and genistein on the hippocampal expression of microRNA-132, IGF-1, and BDNF in type 2 diabetic ovariectomized rats. Materials and Methods: Wistar female rats in the weight range of 180-220 gr (n=10) were assigned to six groups: sham, ovariectomy, ovariectomized diabetic, ovariectomized diabetic treated with genistein for eight weeks, diabetic ovariectomized treated with swimming for eight weeks, and a group that was treated with both genistein and swimming for eight weeks. The effect of those treatments was assessed by the determination of microRNA-132, insulin growth factor 1 (IGF-1), and brain-derived neurotrophic factor (BDNF) expression levels within the hippocampus. These genes were evaluated by real-time-polymerase chain reaction (RT-PCR) and spatial memory was assessed by the Morris water maze. Results: Ovariectomy demonstrated a decrease in the expression of microRNA-132, IGF-1, and BDNF in the hippocampus, as well as spatial memory, in diabetic ovariectomized rats, which showed a greater reduction in the expression of those genes in rats (P<0.05). Nevertheless, genistein administration, swimming training, and a combination of them significantly up-regulated microRNA-132, BDNF, and IGF-1 expression, as well as spatial memory (P<0.05). Conclusions: As evidenced by the obtained results, the combined use of genistein and swimming could prevent estrogen deficiency effects in the hippocampus of ovariectomized diabetic rats

Download Full-text

Different Analgesic Effects of Intrathecal Endomorphin-2 on Thermal Hyperalgesia and Evoked Inflammatory Pain in Ovariectomized Rats

January 2018 - Pain Physician ◽

10.36076/ppj/2015.18.195 ◽

2015 ◽

Vol 2;18 (2;3) ◽

pp. 195-205

Author(s):

Wen Wang

Keyword(s):

Back Pain ◽

Inflammatory Pain ◽

Hormone Replacement ◽

Thermal Hyperalgesia ◽

Female Rats ◽

Ovariectomized Rats ◽

Analgesic Effects ◽

Ovx Rats ◽

Steroid Dependent ◽

Key Words Analgesia

Hormone replacement remains one of the common therapies for menopause-related pain but is associated with risk of orofacial or back pain. Spinal endomorphin-2 (EM-2) is involved in varied pain and its release is steroid-dependent, but whether increasing spinal EM-2 can inhibit thermal hyperalgesia and inflammatory pain in ovariectomized (OVX) female rats, an animal model mimicking menopause, is not clear, nor is the potential involvement of spinal mu-opioid receptor (MOR). In the current study, we revealed that the temporal decrease of spinal EM-2 is accompanied with OVX-induced thermal hyperalgesia that was dose-dependently attenuated by intrathecal (IT) delivery of EM2. The subcutaneous injection of formalin-induced inflammatory pain in OVX rats was exacerbated and IT delivery of EM-2 dose-dependently inhibited the inflammatory pain. However, the ED50 for IT delivery of EM-2 on thermal hyperalgesia is smaller than that on inflammatory pain in OVX rats, suggesting different contributions of the EM-2 system to these 2 pain modalities in OVX rats. IT pretreatment with MOR antagonist, betafunaltrexamine (β-FNA), attenuated IT EM-2 analgesia on both thermal hyperalgesia and inflammatory pain in OVX rats. Furthermore, IT delivery of EM-2 did not affect the animals’ locomotion or anxiety status. Our findings suggested that IT EM-2 might be a safer analgesia strategy than hormone replacement therapy in reducing risk of orofacial or back pain. However, a long-lasting form of EM-2 with less tolerance is needed to induce sustained analgesia. Key words: analgesia, intrathecal, endomorphin, ovariectomize, rat

Download Full-text

Assessment of Superoxide Dismutase and Catalase Evolution in Different Stages of an Experimental Endometriosis

Revista de Chimie ◽

10.37358/rc.17.6.5678 ◽

2017 ◽

Vol 68 (6) ◽

pp. 1381-1383

Author(s):

Allia Sindilar ◽

Carmen Lacramioara Zamfir ◽

Eusebiu Viorel Sindilar ◽

Alin Constantin Pinzariu ◽

Eduard Crauciuc ◽

...

Keyword(s):

Oxidative Stress ◽

Superoxide Dismutase ◽

Antioxidant Enzymes ◽

Reproductive Function ◽

Female Rats ◽

Oxygen Species ◽

Efficient Treatment ◽

Endometrial Cells ◽

Gynecological Disorder ◽

The Impact

Endometriosis is described as a gynecological disorder characterized by the presence of endometrial tissue outside the uterus; extensively explored because of its increasing incidency, with an indubitable diagnostic only after invasive surgery, with no efficient treatment, it has still many aspects to be elucidated. A growing body of facts sustain oxidative stress as a crucial factor between the numerous incriminated factors implicated in endometriosis ethiopathogeny. Reactive oxygen species(ROS) act to decline reproductive function. Our study intends to determine if an experimental model of endometriosis may be useful to assess the impact of oxidative stress on endometrial cells; we have used a murine model of 18 adult Wistar female rats. A fragment from their left uterine horn was implanted in the abdominal wall. After 4 weeks, a laparatomy was performed, 5 endometrial implants were removed, followed by biochemical tissue assay of superoxide dismutase(SOD) and catalase(CAT). At the end of the experiment, the rats were sacrificed, the implants were removed for histopathological exam and biochemical assay of antioxidant enzymes. The results revealed decreased levels of antioxidant enzymes, pointing on significant oxidative stress involvement.

Download Full-text