Estrogen-dependent regulation of neurokinin 3 receptor-mediated uterine contractility in the rat

The receptors for neurokinin 1 (NK1-R), neurokinin 2 (NK2-R), and neurokinin 3 (NK3-R) are expressed and functionally active in the uterus, promoting strong contractions of the myometrium. Previously, we demonstrated that myometrial contractility activated by the NK-Rs is regulated by estrogen. In the current study, we furthered our investigations of the role of estrogen in the regulation of NK3-R-mediated myometrial contractility. Estrogen promotes both heterologous and homologous desensitization of NK3-R-mediated uterine contractility. In tissue obtained from estrogen-dominated rats (ovariectomized estrogen-treated rats and rats in estrus), the magnitude of uterine contractions decreased in response to consecutive additions of the NK3-R-selective agonist senktide. By addition of the fourth dose of agonist, the contractile response was routinely barely above baseline. In contrast, in tissue obtained from non-estrogen-dominated rats consecutive doses of senktide resulted in contractions of identical magnitude. The homologous desensitization was specific to the NK3-R, and the desensitization of the NK3-R-mediated response did not affect the magnitude or nature of uterine contractions in response to NK1-R or NK2-R activation. Furthermore, heterologous and homologous desensitization of NK3-R-mediated contractility is dependent upon the duration of exposure to estrogen. This complex mechanism appears to be important in intact tissue; capsaicin-mediated release of endogenous neuropeptides resulted in a desensitization of response to subsequent stimulation with senktide in estrogen-dominated uterine tissue.     

The ovarian and cervical regions of the rat uterus display a different contractile response to serotonin and prostaglandin F2alpha. I. The estrous cycle

In pharmacological studies using isolated tissues, the sensitivity to different agonists may vary depending on the anatomical region. The aim of the present study was to evaluate the in vitro contractile response to serotonin, prostaglandin F2alpha, and oxytocin of the ovarian and the cervical uterine segments isolated from rats in the four different stages of the rat estrous cycle. Non-cumulative curves were recorded for both, the ovarian and the cervical uterine segments. The cervical portion displayed a higher contractile response to serotonin and a lower response to PGF2alpha than the ovarian portion. Oxytocin induced similar responses in both uterine segments. The uterine ovarian segment displayed a similar sensitivity to serotonin in all the estrous cycle stages, whereas in the cervical segment, influenced by estrogens in diestrus and proestrus, an increase in contractility was observed. According to these findings, serotonin might participate in the spermatozoa transport toward the oviduct. The higher response of the ovarian portion to prostaglandin F2alpha is in line with its role during labor and delivery.     

Estrous changes in vaginal nociception in a rat model of endometriosis

A rat model of endometriosis, in which pieces of uterine horn (versus fat in controls) are autotransplanted into the abdomen where they form cysts, reduces fecundity and produces vaginal hyperalgesia. The cysts gradually enlarge over a 2-month period postsurgically and then plateau. Cysts regress with low estrogen levels and reappear when they rise. Based on the hypothesis that the vaginal hyperalgesia depends upon the cysts, this study tested two predictions: that (1) the hyperalgesia would develop postsurgically in parallel with the cysts, and (2) the hyperalgesia would vary with estrous, being greatest when estrogen levels are high (proestrus) and least when low (estrus). In rats trained to escape vaginal distention, percentage escape responses to different distention volumes were measured across the rat's 4-day estrous cycle for 2.5 months before and up to 4 months after autotransplantation of uterus (n=9) or fat (n=6) in abdominal sites. Vaginal pressures were also measured. In rats with uterine but not fat autotransplants, escape percentages increased postsurgically over a 2-month period and then plateaued. The increase was greatest in proestrus and failed to occur in estrus. Vaginal pressures were unchanged in all groups. These results strongly support the hypothesis that the vaginal hyperalgesia depends upon the cysts. Because the cysts were located in sites remote from the vagina, the hyperalgesia involves viscero-visceral interactions and is likely centrally mediated, whereas the estrous modulation could involve hormonal actions either on the cysts or, more likely, on vaginal afferent fibers, and/or on central neurons.     

Opposite regulation of XIAP and Smac/DIABLO in the rat endometrium in response to 17β-estradiol at estrus

During rat estrous cycle, the endometrium proliferates in response to sex steroids and specific endometrial epithelial cells undergo apoptosis in absence of embryonic factors. The central executioner of apoptosis is a family of aspartic acid-specific cysteine proteases known as caspases. Smac/DIABLO is released from the mitochondria during apoptosis and its stimulation promotes caspases activation by neutralizing members of the inhibitor of apoptosis proteins (IAPs) family, such as X-linked inhibitor of apoptosis protein (XIAP). The aim of this study was to investigate the involvement of Smac/DIABLO and XIAP in the control of caspases activation in endometrium of cycling rats. Polyoestrus female rats were sacrificed at each stage of estrous cycle (diestrus, proestrus, estrus, and metestrus). Endometrial protein extracts were collected to perform Western Blot analysis. Alternatively, uterine horns were sectioned for immunohistochemistry (IHC). We and others showed previously the presence of apoptosis at estrus in rat uterine epithelium. In the present study, cleaved caspase-3, -6, and -7 fragments were detected at estrus. IHC confirmed that caspase-3 was present only in luminal and glandular epithelium at estrus. XIAP was highly expressed at estrus in both epithelial and stromal cells. In contrast, expression of Smac/DIABLO was elevated at diestrus, proestrus and metestrus but was minimal at estrus. Treatment of ovariectomized rats with 17β-estradiol induced XIAP expression and inhibited Smac/DIABLO protein expression in the endometrium. Cleaved caspase-3, -6, and -7 fragments increased in endometrial protein extracts following 17β-estradiol treatment. Expression of NF-κB and IκB proteins, and IκB phosphorylation status were detected in the endometrium but were not influenced by the estrous cycle. These findings suggest that Smac/DIABLO and XIAP are regulated differently and may play important roles in the regulation of endometrial cell fate. Moreover, this study confirms a key role for executioner caspases in the control of apoptotic processes at estrus in the rat uterus.     

Effects of acute and chronic restraint and estrus cycle on pituitary-adrenal function in the rat

Female Long-Evans hooded rats with 5-day estrus cycles were subjected to 4 hr of continuous restraint for either 1 or 20 days. On the last day of the stress regimen, plasma and adrenal corticosterone concentrations were determined and classified according to the stage of the estrous cycle. The results indicated that acute stress produced greater plasma corticosterone concentrations than controls only during estrus, whereas in response to chronic stress significant stress-induced increments were observed during estrus and proestrus. The results suggest that the estrous cycle influences the magnitude of the stress-induced increments for both acute and chronic stress. In addition, the pituitary-adrenal system did not show habituation to repeated administration of this stress, but sensitization was observed during proestrus.     

基质金属蛋白酶-2、-9及其组织抑制因子(TIMPs)在动情周期大鼠子宫中的表达(英文)

基质金属蛋白酶（ＭＭＰｓ）家族的作用是降解所有细胞外基质,其活性受其特异性组织抑制因子（ＴＩＭＰｓ）的抑制。细胞外基质成分的降解与重组在动物生殖生长过程中起重要作用,其变化可以通过ＭＭＰｓ和ＴＩＭＰｓ两者表达水平的变化进行监测。大鼠虽然没有月经形成,但是在其子宫内膜也出现类似灵长类的生殖生物学变化。本文从ＭＭＰｓ和ＴＩＭＰｓ两者的表达水平,对大鼠子宫内膜的这些变化进行了研究。于大鼠动情周期的不同时期,将其处死、取子宫制备酶粗提液和组织切片,采用酶谱法（ｚｙｍｏｙｒａｎｈｎ）和原位杂交方法研究动情周期大鼠子宫中ＭＭＰ－２和－９的活性变化以及ＭＭＰ－２、－９和ＴＩＭＰ－１、－２、－３ｍＲＮＡ的表达。并通过光密度扫描方法对酶谱结果进行半定量分析。所用杂交探针见Ｔａｂｌｅ１。酶谱结果显示：在动情周期大鼠子宫中只检测到６７ｋＤａ的ＭＭＰ－２活性,而没有检测到ＭＭＰ－９的活性（Ｆｉｇ．１）。ＭＭＰ－２的活性在动情前期最高,动情期和动情后期次之,间情期最低（Ｆｉｇ．２）。原位杂交结果显示：ＭＭＰ－２、－９、ＴＩＭＰ－１、－２、－３ｍＲＮＡ主要在子宫内膜基底部的基质细胞中表达。ＭＭＰ－２和－９ｍＲＮＡ在动情前期、动情期和动     

Effects of thymulin and GnRH on the release of gonadotropins by in vitro pituitary cells obtained from rats in each day of estrous cycle

The effects of thymulin and GnRH on FSH and LH release were studied in suspension cultures of anterior pituitary cells from female adult rats sacrificed on each day of the estrous cycle. The spontaneous release of gonadotropins by pituitaries, as well as their response to GnRH or thymulin addition, fluctuated during the estrous cycle. Adding thymulin to pituitary cells from rats in diestrus 1 increased the concentration of FSH; while in cells from rats in estrus, FSH level decreased. Thymulin had a stimulatory effect on the basal concentration of LH during most days of the estrous cycle. Adding GnRH increased FSH release in cells from rats in diestrus 1, diestrus 2, or proestrus, and resulted in higher LH levels in cells obtained from rats in all days of the estrous cycle. Compared to the GnRH treatment, the simultaneous addition of thymulin and GnRH to cells from rats in diestrus 1, diestrus 2, or proestrus resulted in lower FSH concentrations. Similar results were observed in the LH release by cells from rats in diestrus 1, while in cells from rats in proestrus or estrus, LH concentrations increased. A directly proportional relation between progesterone serum levels and the effects of thymulin on FSH release was observed. These data suggest that thymulin plays a dual role in the release of gonadotropins, and that its effects depend on the hormonal status of the donor's pituitary.     

Interaction of 4-hydroxylated estradiol and potential-sensitive Ca2+ channels in altering uterine blood flow during the estrous cycle and early pregnancy in gilts

This study was conducted to define further the role of catechol estrogens (CE) as intermediates in estrogen-stimulated uterine hyperemia. Previous studies from our laboratory strongly suggest that changes in uterine blood flow (UBF) result from alterations in uterine arterial tone (distensibility) and/or contractility (reactivity to alpha 1-adrenergic agonists). Tone changes appear to set the baseline rate of flow, whereas contractility changes result in short-term reductions in luminal diameter. Changes in uterine arterial tone and contractility result from alterations in Ca2+ uptake through potential-sensitive channels (PSCs) and receptor-operated channels (ROCs), respectively. Uterine and mesenteric arteries were removed from 6 gilts at estrus (Day 0), 9 gilts on Day 13 of gestation (high estrogen, high UBF), and 8 gilts on Day 13 of the estrous cycle (low estrogen, low UBF). Arterial measurements included initial tone (baseline perfusion pressure [BPP] to a constant intraluminal flow) and increased tone after exposure to KCl, the contractility in response to the alpha 1-agonist phenylephrine, and specific uptake of 45Ca before and after exposure to the CE 4-hydroxylated estradiol (4OH-E2). Contractility of uterine arteries from Day 13 nonpregnant (NP) and Day 13 pregnant (P) gilts to phenylephrine were similar and significantly greater (p less than 0.01) than contractility of vessels from estrous gilts. The BPP and responses of uterine arteries from Day 13 NP gilts to KCl were greater (p less than 0.05) than the BPP and responses of arteries from Day 13 P and estrous gilts, which were similar to each other.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biochemical analysis of female mice urine with reference to endocrine function: a key tool for estrus detection

Species-specific chemical signals released through urine, sweat, saliva and feces are involved in communication between animals. Urinary biochemical constituents along with pheromones may contribute to variation across reproductive cycles and facilitate to estrus detection. Hence, the present study was designed to analyze such biochemical profiles, such as proteins, carbohydrates, lipids, fatty acids, in response with steroid hormones such as estradiol and progesterone. The experimental groups were normal, prepubertal, ovariectomized, and ovariectomized with estrogentreated female mice. In normal mice, the protein and lipid concentrations in urine were significantly higher in proestrus and estrus phases and the quantity of fatty acids was also comparatively higher in estrus. Furthermore, certain fatty acids, namely tridecanoic, palmitic and oleic acids, were present during proestrus and estrus phases, but were exclusively absent in ovariectomized mice. However, the carbohydrate level was equally maintained throughout the four phases of estrous cycle. For successful communication, higher concentrations of protein and specific fatty acids in estrus are directly involved. The significant increase in estradiol at estrus and progesterone at metestrus seems to be of greater importance in the expression pattern of biochemical constituents and may play a notable role in estrous cycle regulation. Thus, we conclude that the variations observed in the concentration of the biochemical constituents depend on the phase of the reproductive cycle as well as hormonal status of animals. The appearance of protein and specific fatty acids during estrus phase raises the possibility to use these as a urinary indicators for estrus detection.     

Cyclic variation in rats's uterine fluid phosphatase level after administration of lyndral (17 alpha-ethinyl estradiol).

An oral administration of antifertility drug Lyndral (17 alpha-ethinyl estradiol) at doses 5 micrograms/rat/a week for 3 consecutive weeks altered the internal biochemical milieu of uterus, showing a cyclic variation in both acid and alkaline phosphatase of the uterine fluid with high levels being present at proestrus and estrus in control rats. In Lyndral treated rats acid phosphatase showed a tendency to increase in estrus and metestrus rats, whereas alkaline phosphatase increased significantly during proestrus and estrus stages of the cycle. All these altered phosphatase levels in uterine fluid, after Lyndral treatment, gives some insight into the hormonal sensitiveness of these enzymes.     

Expression of ghrelin in the porcine hypothalamo-pituitary-ovary axis during the estrous cycle

Ghrelin, a 28-amino acid acylated peptide produced mainly by the stomach, has various functions. Recent studies focus on its endocrine and/or paracrine effects in the regulation of the hypothalamo-pituitary-gonadal axis, that is, the role in reproduction. Previous data have shown that variation of ghrelin depended on the phases of estrous cycle in adult rat ovary. This study was to investigate the expression of ghrelin in the cyclic porcine hypothalamo-pituitary-ovary axis and stomach by semiquantitative RT-PCR and immunohistochemical method. Twenty virginal gilts were classified into four groups as the proestrus, estrus, diestrus1 and diestrus2. Results showed that expression of ghrelin mRNA in the hypothalamus changed with the estrous cycle, i.e., with the highest level in the proestrus and the lowest in the estrus. In the pituitary, the pattern of ghrelin mRNA expression during estrous cycle markedly decreased in the estrus and diestrus1. In the ovary, ghrelin mRNA exhibited with the highest level in the diestrus2 and the lowest in the proestrus, which was different from those in the hypothalamus and pituitary. In the stomach, the expression of ghrelin mRNA had the same tendency as that of the porcine ovary. In immunohistochemical experiment, ghrelin immunoreactive cells were predominantly located in the luteal compartment and growing follicles in the luteal phase of ovary. However, only few ghrelin immunoreactive cells were found in the proestrus ovary. In gastric mucosa, ghrelin immunoreactive cells were detected in the estrus, diestrus1 and diestrus2, but few ghrelin positive cells were seen in the proestrus. Results suggest that ghrelin may play a major role in the endocrine network that integrates energy balance and reproduction.     

Uterine motor alterations and estrous cycle disturbances associated with colonic inflammation in the rat

The impact of colitis on uterine contractility and estrous cycle was investigated after intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. Colitis severity was assessed by macroscopic damage scoring (MDS) 4 days after TNBS, and myeloperoxidase (MPO) activity was measured in both colon and uterus of control and colitic rats. Estrous cycle stages were determined by vaginal smears and histology, and uterine contractility was assessed in vitro on longitudinal and circular strips. In control rats, uterine MPO activity varied markedly during the cycle and peaked around estrus. In rats with moderate colitis [MDS < 5, 3.1 +/- 0.2 (mean +/- SE)], uterine MPO decreased by 61% compared with estrus control, without disruption of the cycle. Frequency of spontaneous contractions was reduced by 32% in circular muscle. Contractile responses to KCl and carbachol were not affected, whereas maximal response to oxytocin decreased by 47% in the longitudinal muscle. In rats with severe colitis (MDS > 5, 6.0 +/- 0.2), uterine MPO was reduced by 96% and estrous cycle was disrupted. Spontaneous contractility was impaired in circular strips, and a 39% decrease in the contraction frequency occurred in the longitudinal strips. Circular strips did not contract to KCl or carbachol; however, longitudinal strips had maximal responses to KCl, carbachol, and oxytocin reduced by 36%, 27%, and 46%, respectively. Estrogen replacement protected the uterine responses to carbachol in colitic rats, whereas oxytocin responses remained depressed. These data indicate that colonic inflammation can influence both spontaneous and evoked uterine contractility, in relation to estrous cycle disturbances, impaired estradiol production, and functional alterations of myometrial cells.     

Spinal effects of oxytocin on uterine motility in anesthetized rats

The rat uterus receives an innervation from the lumbosacral and thoracolumbar segments of the spinal cord. These segments receive descending oxytocinergic projections from the paraventricular nucleus of the hypothalamus. We tested the hypothesis that oxytocin regulates uterine motility through a spinal site of action. Oxytocin was administered in anesthetized female rats either intrathecally at the lumbosacral or thoracolumbar spinal cord levels or intravenously. Uterine activity was revealed by measuring changes of intrauterine pressure using an indwelling balloon placed in one caudal uterine horn. The uterus displayed a spontaneous activity characterized by intrauterine pressure rises, the frequency, amplitude, and duration of which were dependent on the stage of the estrous cycle. Oxytocin delivered at the lumbosacral level affected the frequency (during proestrus, estrus, and diestrus) and amplitude (during proestrus and estrus) of uterine activity. During estrus, oxytocin delivered at the thoracolumbar level affected the frequency, amplitude, and duration of the intrauterine pressure rises. Intravenous oxytocin not only affected intrauterine pressure rises (namely amplitude during proestrus and estrus and frequency and duration during estrus) but also increased the basal tone during estrus. The effects of lumbosacral oxytocin were partly mimicked by the oxytocin agonist [Thr(4),Gly(7)]-oxytocin blocked by the oxytocin receptor antagonist atosiban and by hexamethonium. Arginine vasopressin delivered at the lumbosacral level had no effect. These results support our hypothesis that oxytocin released by descending paraventriculo-spinal pathways and acting on spinal oxytocin receptors modulates the activity of the uterus. This regulation is cycle dependent.     

Oxytocin and glucose oxidation in the rat uterus

The effects of oxytocin on the biochemical pathways of glucose oxidation were investigated in the rat uterus. In the presence of oxytocin, glucose oxidation in uterine segments obtained from Sprague-Dawley rats at diestrus increased 1.5–2.0-fold above the basal rate. A half-maximal response was observed at about 3 nM oxytocin; the maximum response was equal to or greater than the response to 1.7 nM insulin. In stripped myometrial segments (denuded of the endometrial component), oxytocin stimulated glucose oxidation at estrus only; whereas in intact uterine segments, the stimulation of oxidation was observed at both estrus and diestrus. In contrast, stimulation of oxidation by carbachol in stripped myometrial segments was independent of the estrous state of the tissue. The ratio of [1-¹⁴C]glucose to [6-¹⁴C]glucose oxidation was measured to estimate the relative involvement of the pentose phosphate and the tricarboxylic acid pathways of metabolism. In myometrial tissue, stimulation of glucose oxidation by oxytocin appeared to proceed through the tricarboxylic acid cycle. In intact uterine segments, at diestrus, glucose oxidation involved largely the pentose phosphate pathway (suggesting increased glucose metabolism in endometrial tissue), whereas at estrus, in the intact tissue segments, oxytocin increased glucose oxidation largely via the tricarboxylic acid cycle, and appeared to do so predominantly in the myometrial tissue. Carbachol-stimulated glucose oxidation appeared to proceed mainly via the tricarboxylic cycle in the myometrial tissue, irrespective of the stage of the estrous cycle. In the uterus of the Brattleboro rat (either intact uterine segments or stripped myometrial strips), oxytocin stimulated glucose oxidation only at estrus, predominantly through the tricarboxylic acid cycle. These findings suggest that oxytocin, in addition to its known effect on the contractility of uterine and myoepithelial smooth muscle, may regulate glucose metabolism in both the myometrial and endometrial components of uterine tissue.     

gamma-Aminobutyric acid activity in the olfactory bulb of the rat during the sexual cycle and response to olfactory stimuli.

Glutamic acid decarboxylase activity in the main and accessory olfactory bulbs throughout the sexual cycle of the rat was studied. The effect of male pheromonal secretion on enzyme activity during proestrus and estrus day was also tested. The enzyme activity showed circadian rhythm during the estrous cycle. This rhythm was disrupted during diestrus-2 afternoon in the main bulb and came back during proestrus afternoon. A different pattern of enzyme activity was present in the accessory bulb, since the circadian rhythm was altered during proestrus morning, returning during estrus afternoon. Male odor exposition did not change enzyme profile activity during proestrus day and during estrus morning in the main bulb. In contrast, in the accessory bulb the olfactory stimuli induced opposite changes to that found in rats from the vivarium during proestrus. Comparison of enzyme activity in olfactory stimuli-deprived rats with that of pheromone-stimulated rats during proestrus showed that male odor exposure specifically affects accessory bulb enzyme activity. It is concluded that the changes of the olfactory bulb GABAergic system during proestrus and estrus day, or that evoked by odor stimuli, demonstrate the discriminative response of this system between the accessory olfactory bulb and the main olfactory bulb.     

Pharmacological receptors for substance P and neurokinins

The three neurokinins identified in mammals, substance P, neurokinin A and neurokinin B, as well as their C-terminal biologically active fragments, have been used to characterize the responses of a variety of isolated organs. Three preparations selective either for substance P (the dog carotid artery), or for neurokinin A (the rabbit pulmonary artery) or for neurokinin B (the rat portal vein) are described. A neurokinin receptor classification is attempted using the neurokinins and their fragments to determine the order of potency of agonists. Three receptor subtypes have been identified: the NK-P, on which substance P (SP) is more active than neurokinin A (NKA) and neurokinin B (NKB), and the neurokinins are more active than their respective fragments; the NK-A on which NKA greater than NKB greater than SP, and some NKA fragments are more discriminative than their precursor; the NK-B on which NKB greater than NKA greater than SP, and fragments of NKB are less active than their precursor. Among the peptides studied, some potent compounds have been identified that could provide selective receptor ligands.     

Variations in free secretory component levels in mucosal secretions of the rat

The present studies were conducted to compare the levels of free secretory component (SC) in a number of rat mucosal secretions and to determine whether SC content varies significantly during the four stages of the estrous cycle. Levels of SC, as measured by radioimmunoassay, were markedly different in various external secretions. Bile contained the highest amount, irrespective of whether SC was normalized to volume or protein. Concentrations of SC in saliva or uterine fluid from intact rats were approximately 20- to 30-fold less than measured in bile. When SC levels were normalized to protein, the SC to protein ratios in uterine, vaginal, and respiratory secretions were six to 18 times greater than values calculated in salivary and small intestinal fluids. Analysis of SC levels in mucosal secretions during the estrous cycle indicated significant variations occur in uterine and vaginal samples, but not in saliva or small intestinal secretions. In the uterine lumen, SC levels were highest at proestrus, partially elevated at estrus, and lowest at both days of diestrus. In contrast, vaginal SC levels were maximal at estrus and reduced at all other stages of the cycle. Immunoglobulin A content was also measured in uterine and vaginal secretions during the estrous cycle. Significant changes in IgA levels were found and these coincided with the changing pattern of SC. These results suggest hormones may modulate SC levels in reproductive tissues. In addition, our findings indicate variations in SC during the estrous cycle may direct the movement of IgA from tissue to lumen.     

Hormonal oscillations during the estrous cycle influence the morphophysiology of the gerbil (Meriones unguiculatus) female prostate (skene paraurethral glands)

The hormonal oscillations that occur during the female reproductive cycle influence the morphophysiology of several organs of the reproductive system. The female prostate is a functional organ sensitive to the action of steroidal hormones, but it is not known whether the hormonal oscillations that occur during the reproductive cycle can alter the biology of this gland. Thus, the present work aims to evaluate the morphofunctional aspects of the female prostate during the gerbil estrous cycle. For this purpose, morphological, morphometric-stereological, serological, and immunocytochemical analyses were carried out. The results of the present study show that the hormonal oscillations that occurred during the estrous cycle altered both the structure and functionality of the gerbil female prostate. These alterations include increased prostatic growth and augmented secretory activity during the proestrus and estrus phases and a gradual decrease of the secretory activity and glandular development in the diestrus I and II phases. These cyclical oscillations appear to be determined by the hormonal peaks of estrogen in diestrus II and by the high levels of progesterone during estrus, since the androgen levels remained constant throughout the estrous cycle.     

Amygdala activation by corticosterone alters visceral and somatic pain in cycling female rats

Irritable bowel syndrome (IBS) is often seen in women, and symptom severity is known to vary over the menstrual cycle. In addition, activation of the hypothalamic-pituitary-adrenal (HPA) axis enhances symptomology and patients with IBS have increased activation of the amygdala, a brain region known to facilitate HPA output. However, little is known about the effects of amygdala activation during different stages of the menstrual cycle. We therefore investigated the effects of amygdala activation on somatic and visceral pain perception over the rat estrous cycle. Female Wistar rats were implanted with either corticosterone (Cort) or cholesterol as a control onto the dorsal margin of the central amygdala. Visceral sensitivity was quantified by recording the visceromotor response (VMR) to colorectal distension (CRD) and somatic sensitivity was assessed via the Von Frey test. In cholesterol controls, both visceral and somatic sensitivity varied over the estrous cycle. Rats in proestrus/estrus responded to CRD with an increased VMR compared with rats in metestrus/diestrus. Somatic sensitivity followed a similar pattern with enhanced sensitivity during proestrus/estrus compared with metestrus/diestrus. Elevated amygdala Cort induced visceral hypersensitivity during metestrus/diestrus but had no effect during proestrus/estrus. In contrast, elevated amygdala Cort increased somatic sensitivity during both metestrus/diestrus and proestrus/estrous. These results suggests that amygdala activation by Cort eliminates spontaneously occurring differences in visceral and somatic pain perception, which could explain the lowered pain thresholds and higher incidence of somatic pain observed in women with IBS.