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Hypertension (Dallas, Tex. : 1979) Aug 2009Female mice are protected from the cerebrovascular dysfunction induced by angiotensin II (Ang II), an effect attributed to estrogen. We examined whether such... (Comparative Study)
Comparative Study
Female mice are protected from the cerebrovascular dysfunction induced by angiotensin II (Ang II), an effect attributed to estrogen. We examined whether such cerebrovascular protection from Ang II is related to the estrous cycle. Cerebral blood flow was monitored by laser-Doppler flowmetry in anesthetized (urethane-chloralose) C57BL/6 female mice equipped with a cranial window. The phase of the estrous cycle was determined by vaginal smear cytology and plasma estrogen measurement. Ang II (0.25 microg/kg per minute, IV, 30 to 45 minutes) elevated arterial pressure (15 to 20 mm Hg) equally across the estrous cycle. However, in proestrus and estrus, phases in which estrogen is relatively high, Ang II did not impair the increase in the cerebral blood flow induced by neural activity or by endothelium-dependent vasodilators (P>0.05 from vehicle). In contrast, in diestrus (lower estrogen), Ang II induced a marked cerebrovascular dysfunction comparable to that of male mice. For example, the cerebral blood flow responses to whisker stimulation and to the endothelium-dependent vasodilator acetylcholine were attenuated by 41+/-12% and 49+/-12%, respectively (P<0.05; n=6 per group). The protection from the cerebrovascular effects of Ang II in proestrus was abolished by the estrogen receptor inhibitor ICI182,780. Ang II also increased production of free radicals in cerebral blood vessels in diestrus (+116+/-13%; P<0.05) but not in proestrus and estrus (P>0.05 from control). Topical treatment with ICI182,780 reestablished Ang II-induced oxidative stress in proestrus (P>0.05 from diestrus). We conclude that the protection from the neurovascular dysfunction induced by acute administration of Ang II in females depends on the estrous cycle and may underlie the increased propensity to cerebrovascular damage associated with low estrogen states.
Topics: Analysis of Variance; Angiotensin II; Animals; Blood Pressure; Cerebrovascular Circulation; Cerebrovascular Disorders; Disease Models, Animal; Endothelium-Dependent Relaxing Factors; Estrogen Receptor alpha; Estrous Cycle; Female; Free Radicals; Laser-Doppler Flowmetry; Male; Mice; Mice, Inbred C57BL; Neocortex; Oxidative Stress; Probability; Random Allocation; Reference Values; Risk Factors; Sensitivity and Specificity; Sex Factors
PubMed: 19506098
DOI: 10.1161/HYPERTENSIONAHA.109.133249 -
Reproductive Biology and Endocrinology... Feb 2010Rats made hypothyroid with propilthyouracil start showing abnormal cycling on the second cycle after the start of the treatment, with a high proportion of spontaneous...
BACKGROUND
Rats made hypothyroid with propilthyouracil start showing abnormal cycling on the second cycle after the start of the treatment, with a high proportion of spontaneous pseudopregnancies and reduced fertility.
METHODS
To investigate some of the mechanisms involved in these reproductive abnormalities, hypothyroidism was induced in virgin rats by propilthyouracil (0.1 g/L in the drinking water) and we determined circulating hormones by radioimmunoassay and whole ovary expression of ovarian hormone receptors, growth factors and steroidogenic enzymes using semi-quantitative RT-PCR.The study was performed on days 6 to 9 of treatment, corresponding to diestrus I (at 20.00-22.00 h), diestrus II (at 20.00-22.00 h), proestrus and estrus (both at 8.00-10.00 h and 20.00-22.00 h) of the second estrous cycle after beginning propilthyouracil treatment. Another group of rats was mated on day 8 and the treatment continued through the entire pregnancy to evaluate reproductive performance.
RESULTS
Hypothyroidism increased circulating prolactin and estradiol on estrus 5 to 7-fold and 1.2 to 1.4-fold respectively. Growth hormone and insulin-like growth factor 1 diminished 60 and 20% respectively on proestrus morning. Hypothyroidism doubled the ovarian mRNA contents of estrogen receptor-beta on proestrus and estrus evenings, cyp19A1 aromatase mRNA on estrus evening and of growth hormone receptor on proestrus evening. Hypothyroidism did not influence ovulation rate or the number of corpora lutea at term, but a diminished number of implantation sites and pups per litter were observed (Hypothyroid: 11.7 +/- 0.8 vs.
CONTROL
13.9 +/- 0.7).
CONCLUSIONS
Short term hypothyroidism alters normal hormone profile in the cycling rat increasing the expression of estrogen receptor-beta and cyp19A1 aromatase on estrus, which in turn may stimulate estradiol and prolactin secretion, favouring corpus luteum survival and the subsequent instauration of pseudopregnancy.
Topics: Animals; Embryo Implantation; Estrous Cycle; Female; Gonadal Steroid Hormones; Growth Hormone; Hypothyroidism; Insulin-Like Growth Factor I; Male; Ovary; Ovulation; Pregnancy; Prolactin; Propylthiouracil; Rats; Rats, Wistar; Thyroid Hormones; Time Factors
PubMed: 20149258
DOI: 10.1186/1477-7827-8-14 -
Endocrinology Jun 2013Female obesity is associated with insulin resistance, hyperandrogenemia, and reproductive dysfunction. We hypothesized that elevated free fatty acids (FFAs) might...
Free fatty acids induce Lhb mRNA but suppress Fshb mRNA in pituitary LβT2 gonadotropes and diet-induced obesity reduces FSH levels in male mice and disrupts the proestrous LH/FSH surge in female mice.
Female obesity is associated with insulin resistance, hyperandrogenemia, and reproductive dysfunction. We hypothesized that elevated free fatty acids (FFAs) might directly modulate pituitary gonadotropin production. FFAs caused a time- and dose-dependent increase in phosphorylation of the MAPKs p38MAPK, c-Jun N-terminal kinase (JNK)-1/2, and ERK1/2 in LβT2 gonadotrope cells. Furthermore, FFAs up-regulated Lhb mRNA expression acutely, an effect that was blocked by JNK inhibition, but suppressed Fshb mRNA expression, an effect that was independent of MAPK signaling. FFAs enhanced the activation of the MAPKs in the presence of GnRH, although the cotreatment did not alter Lhb induction but did eliminate the GnRH induction of Fshb. FFAs also suppressed activin-induced Fshb expression. Knockdown experiments showed that the FFA effect on the inflammatory kinases p38MAPK and JNK and on Lhb, but not Fshb, mRNA expression is mediated via toll-like receptor-2 and toll-like receptor-4 and was mimicked by lipopolysaccharide stimulation. In vivo, male C57BL/6 mice on a high-fat diet showed reduced FSH levels consistent with the suppression of Fshb seen in vitro. Histological analysis of the testes showed an increased number of abnormal seminiferous tubules. Female mice on a high-fat diet lacked the expected proestrus LH and FSH surge and exhibited an increase in the number of days at estrus and a reduced number of days at proestrus, and ovaries had significantly fewer corpora lutea. Taken together, our findings suggest that lipid excess can lead to reproductive defects in both male and female mice.
Topics: Animals; Diet, High-Fat; Dose-Response Relationship, Drug; Fatty Acids, Nonesterified; Female; Follicle Stimulating Hormone, beta Subunit; Gene Expression; Gonadotrophs; Immunoblotting; Luteinizing Hormone, beta Subunit; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Obesity; Ovary; Pituitary Gland; Proestrus; RNA Interference; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Toll-Like Receptor 2; Toll-Like Receptor 4
PubMed: 23525221
DOI: 10.1210/en.2012-2218 -
Journal of Integrative Neuroscience Mar 2021The social behavior mechanisms have not been thoroughly reported in the solitary female striped dwarf hamster (). In this study, the handling bag test and neutral arena...
The social behavior mechanisms have not been thoroughly reported in the solitary female striped dwarf hamster (). In this study, the handling bag test and neutral arena measurements were used to detect the changes of aggression in the face of rivals of different genders of wild striped dwarf hamsters. We found that female hamsters had the highest aggressive performance in proestrus, followed by estrus, and the lowest in metestrus and the dioestrus, and the increased aggression during the proestrus or estrus period was low-intensity aggression such as intimidation, shock, boxing and counterattack, or even ritualized non-harmful behaviors to drive away opponents. When confronted with male individuals, aggression in females decreased significantly during estrus. The concentration of plasma estradiol was the highest in estrus and the lowest in metestrus and dioestrus. In contrast, estrogen receptor 2 relative expression in the hypothalamus is the lowest in proestrus and highest in metestrus and dioestrus. Besides, both estradiol levels in plasma and estrogen receptor 2 mRNA in the hypothalamus were associated with aggression. These results will broaden our understanding of the molecular mechanism of how breeding phenotype is an essential driver in changing the social behavior of female .
Topics: Aggression; Animals; Behavior, Animal; Cricetinae; Estradiol; Estrogen Receptor beta; Estrous Cycle; Female; Hypothalamus; Male; Social Behavior
PubMed: 33834693
DOI: 10.31083/j.jin.2021.01.302 -
Reproduction in Domestic Animals =... Oct 2022The aim of this study was to assess whether vulvar morphometric changes occurring in female pigs during proestrus and oestrus could be objective, accurate and predictive...
The aim of this study was to assess whether vulvar morphometric changes occurring in female pigs during proestrus and oestrus could be objective, accurate and predictive indicators of the onset to oestrus and thus performed artificial inseminations at the most appropriate time. For that purpose, pictures of vulvas from 60 hyperprolific females (30 gilts and 30 sows) during proestrus and oestrus were taken once a day. Vulva measurements (area, perimeter, length and width) on these pictures were performed using the image processing ImageJ software. Gilts and sows showed statistical differences (p < .01) in all vulvar morphometric measurements between proestrus and oestrus. Statistical differences in vulvar metrics were detected 24 h before the onset to oestrus, affecting all vulvar measurements in gilts, whereas only vulvar width was affected in sows. The image analysis used in this study may contribute to the development of smart technology in swine farming.
Topics: Animals; Estrus; Female; Insemination, Artificial; Proestrus; Sus scrofa; Swine; Vulva
PubMed: 35689465
DOI: 10.1111/rda.14178 -
Archives of Razi Institute Aug 2023Ginseng is known as the king of all herbs in terms of antioxidant and anti-inflammatory activities and recently has become more involved in the treatment of neurological...
Ginseng is known as the king of all herbs in terms of antioxidant and anti-inflammatory activities and recently has become more involved in the treatment of neurological diseases. In this regard, this study aimed to determine the effects of on pentylenetetrazol-induced epilepsy during the estrus cycle. For this purpose, 30 rats were randomly divided into five groups, namely control (saline), valproic acid (VPA, 75 mg/kg), (50 mg/kg), (100 mg/kg), and (150 mg/kg) with four subgroups (proestrus, estrus, metestrus, and diestrus). Subsequently, the initiation time of myoclonic seizures (ITMS), initiation time of tonic-clonic seizures (ITTS), and seizure duration (SD) were determined. According to the results, ITMS and ITTS significantly increased in the VPA-treated group (<0.05). (100 and 150 mg/kg) administration significantly increased ITMS and ITTS (<0.05). Moreover, the ITMS and ITTS in -treated rats were significantly higher in luteal phases, compared to the follicular phase (<0.05). In addition, pretreatment with VPA significantly decreased SD, compared to the control group (<0.05). A significant decrease in SD was observed in the rats pretreated with (100 and 150 mg/kg) (<0.05). Seizure duration significantly decreased in animals that received in luteal phases, compared to the follicular phase (<0.05). These results suggested that have anticonvulsant effects that are more prominent during the luteal phase than the follicular phase.
Topics: Animals; Female; Rats; Anticonvulsants; Estrus; Ginsenosides; Pentylenetetrazole; Seizures; Valproic Acid
PubMed: 38226383
DOI: 10.32592/ARI.2023.78.4.1359 -
Journal of Psychopharmacology (Oxford,... Dec 2022Cannabidiol (CBD), the major non-psychoactive constituent of cannabis, has therapeutic potential for the treatment of anxiety. Most preclinical studies investigate only...
RATIONALE
Cannabidiol (CBD), the major non-psychoactive constituent of cannabis, has therapeutic potential for the treatment of anxiety. Most preclinical studies investigate only acute effects of CBD and only in males, yet the drug is most likely to be used over a sustained period in clinical practice.
OBJECTIVES
The objectives of this study were to investigate the anxiolytic-like effect of CBD in female rats compared to males and to determine whether the responsiveness of females was influenced by the stage of the estrous cycle.
METHODS
We carried out experiments to compare the effect of CBD in male and female rats in the elevated plus maze (EPM) in response to acute and short-term (4 days) administration through a complete cycle in females.
RESULTS
Male and female rats behaved in a similar manner in the EPM, but females in the late diestrus (LD) phase exhibited more anxiety-like behavior than at other stages, the difference reaching statistical significance compared to proestrus stages. CBD produced anxiolytic-like effects in both sexes, but female rats were responsive only in LD and 10-fold lower dose than males. After sub-chronic (4 days) treatment, responsiveness to CBD was maintained in females in LD, but females in proestrus remained unresponsive to CBD treatment.
CONCLUSIONS
We suggest that there are sex differences in the anxiolytic-like effects of CBD in rats that reflect different underlying mechanisms: based on literature data, gonadal hormone status linked to GABA receptor expression in females, and 5-HT receptor activation in males.
Topics: Female; Male; Rats; Animals; Anti-Anxiety Agents; Cannabidiol; Elevated Plus Maze Test; Sex Characteristics; Rats, Wistar; Anxiety; Receptors, GABA-A
PubMed: 36239039
DOI: 10.1177/02698811221125440 -
PloS One 2011The anterior pituitary is under a constant cell turnover modulated by gonadal steroids. In the rat, an increase in the rate of apoptosis occurs at proestrus whereas a...
The anterior pituitary is under a constant cell turnover modulated by gonadal steroids. In the rat, an increase in the rate of apoptosis occurs at proestrus whereas a peak of proliferation takes place at estrus. At proestrus, concomitant with the maximum rate of apoptosis, a peak in circulating levels of prolactin is observed. Prolactin can be cleaved to different N-terminal fragments, vasoinhibins, which are proapoptotic and antiproliferative factors for endothelial cells. It was reported that a 16 kDa vasoinhibin is produced in the rat anterior pituitary by cathepsin D. In the present study we investigated the anterior pituitary production of N-terminal prolactin-derived fragments along the estrous cycle and the involvement of estrogens in this process. In addition, we studied the effects of a recombinant vasoinhibin, 16 kDa prolactin, on anterior pituitary apoptosis and proliferation. We observed by Western Blot that N-terminal prolactin-derived fragments production in the anterior pituitary was higher at proestrus with respect to diestrus and that the content and release of these prolactin forms from anterior pituitary cells in culture were increased by estradiol. A recombinant preparation of 16 kDa prolactin induced apoptosis (determined by TUNEL assay and flow cytometry) of cultured anterior pituitary cells and lactotropes from ovariectomized rats only in the presence of estradiol, as previously reported for other proapoptotic factors in the anterior pituitary. In addition, 16 kDa prolactin decreased forskolin-induced proliferation (evaluated by BrdU incorporation) of rat total anterior pituitary cells and lactotropes in culture and decreased the proportion of cells in S-phase of the cell cycle (determined by flow cytometry). In conclusion, our study indicates that the anterior pituitary production of 16 kDa prolactin is variable along the estrous cycle and increased by estrogens. The antiproliferative and estradiol-dependent proapoptotic actions of this vasoinhibin may be involved in the control of anterior pituitary cell renewal.
Topics: Animals; Apoptosis; Cells, Cultured; Estradiol; Estrus; Female; Molecular Weight; Peptide Fragments; Pituitary Gland, Anterior; Prolactin; Rats; Rats, Wistar
PubMed: 21760910
DOI: 10.1371/journal.pone.0021806 -
The Journal of Comparative Neurology May 2023An important factor that can modulate neuron properties is sex-specific hormone fluctuations, including the human menstrual cycle and rat estrous cycle in adult females....
An important factor that can modulate neuron properties is sex-specific hormone fluctuations, including the human menstrual cycle and rat estrous cycle in adult females. Considering the striatal brain regions, the nucleus accumbens (NAc) core, NAc shell, and caudate-putamen (CPu), the estrous cycle has previously been shown to impact relevant behaviors and disorders, neuromodulator action, and medium spiny neuron (MSN) electrophysiology. Whether the estrous cycle impacts MSN dendritic spine attributes has not yet been examined, even though MSN spines and glutamatergic synapse properties are sensitive to exogenously applied estradiol. Thus, we hypothesized that MSN dendritic spine attributes would differ by estrous cycle phase. To test this hypothesis, brains from adult male rats and female rats in diestrus, proestrus AM, proestrus PM, and estrus were processed for Rapid Golgi-Cox staining. MSN dendritic spine density, size, and type were analyzed in the NAc core, NAc shell, and CPu. Overall spine size differed across estrous cycle phases in female NAc core and NAc shell, and spine length differed across estrous cycle phase in NAc shell and CPu. Consistent with previous work, dendritic spine density was increased in the NAc core compared to the NAc shell and CPu, independent of sex and estrous cycle. Spine attributes in all striatal regions did not differ by sex when estrous cycle was disregarded. These results indicate, for the first time, that estrous cycle phase impacts dendritic spine plasticity in striatal regions, providing a neuroanatomical avenue by which sex-specific hormone fluctuations can impact striatal function and disorders.
Topics: Humans; Rats; Female; Male; Animals; Nucleus Accumbens; Dendritic Spines; Rats, Sprague-Dawley; Putamen; Estrous Cycle; Estradiol
PubMed: 36756791
DOI: 10.1002/cne.25460 -
Scientific Reports Aug 2021Stress responses are highly plastic and vary across physiological states. The female estrous cycle is associated with a number of physiological changes including changes...
Stress responses are highly plastic and vary across physiological states. The female estrous cycle is associated with a number of physiological changes including changes in stress responses, however, the mechanisms driving these changes are poorly understood. Corticotropin-releasing hormone (CRH) neurons are the primary neural population controlling the hypothalamic-pituitary-adrenal (HPA) axis and stress-evoked corticosterone secretion. Here we show that CRH neuron intrinsic excitability is regulated over the estrous cycle with a peak in proestrus and a nadir in estrus. Fast inactivating voltage-gated potassium channel (I) currents showed the opposite relationship, with current density being lowest in proestrus compared to other cycle stages. Blocking I currents equalized excitability across cycle stages revealing a role for I in mediating plasticity in stress circuit function over the female estrous cycle.
Topics: Animals; Corticotropin-Releasing Hormone; Estrous Cycle; Female; Hypothalamus; Mice; Neuronal Plasticity; Neurons; Pituitary-Adrenal System; Stress, Physiological
PubMed: 34404890
DOI: 10.1038/s41598-021-96341-4