Influence of the estrous cycle on the sensitivity to catecholamines in right atria from rats submitted to foot-shock stress

We investigated the mechanisms of the alterations in sensitivity to catecholamines in right atria from female rats exhibiting regular 4-day estrous cycles after three foot-shock sessions at estrus, metestrus, and diestrus or at diestrus, proestrus, and estrus. Right atria from stressed rats sacrificed at diestrus showed subsensitivity to noradrenaline and adrenaline. After in vitro sympathetic denervation (38 microM 6-hydroxydopamine) plus inhibition of neuronal reuptake (0.1 microM desipramine) subsensitivity to noradrenaline was abolished, but it was again evident when extraneuronal uptake was also inhibited (10 microM phenoxybenzamine and 30 microM corticosterone). The same pretreatment abolished the subsensitivity to adrenaline. After addition of 1 microM butoxamine, a beta 2-adrenoceptor antagonist, the tissues from stressed rats were subsensitive to adrenaline. Right atria from stressed rats sacrificed at estrus did not show any alteration in sensitivity to catecholamines. We conclude that after foot-shock stress, right atria from female rats sacrificed at diestrus showed subsensitivity of the chronotropic response to catecholamines as a result of a conformational alteration of beta 1-adrenoceptors, simultaneously with an increase in beta 2-adrenoceptor-mediated response. The mechanisms seem to be similar to those which underlie stress-induced alterations in catecholamine sensitivity in right atria from male rats. However, during estrus there are some protective factors that prevent the effects of stress on right atria.     

Variations in uterine innervation during the estrous cycle in rat

Uterine innervation undergoes profound remodeling during puberty, pregnancy, and after parturition. However, the extent to which uterine innervation may change during the estrous cycle is uncertain. The objective of the present study was to determine whether nerve fiber density of the uterine horn is altered during the estrous cycle and, if so, which subpopulations are affected. Immunostaining for the pan-neuronal marker protein gene product (PGP) 9.5 revealed fibers within the vascular zone, myometrium, and endometrium, with greater density in the ovarian and cervical regions than in the middle. In most structures, nerve density was reduced during estrus. This could not be accounted for by increased target volume, as the reduction in longitudinal muscle innervation persisted after correction for changes in target size. Immunostaining for vasoactive intestinal polypeptide-immunoreactive parasympathetic nerves revealed fibers associated predominantly with the vascular zone and circular muscle within the cervical region. No cyclical variation was detected. Calcitonin gene-related peptide-immunoreactive nerves were present within all structures, and density was highest at the ovarian end. These fibers also did not vary significantly through estrous. Dopamine beta-hydroxylase-immunoreactive sympathetic nerves innervated all structures, with greater density in the ovarian end. These fibers were reduced substantially during estrus, but the decline was also significant in proestrus, thus preceding that detected by using the pan-neuronal marker. We conclude that the estrous cycle in rat is accompanied by structural remodeling of sympathetic nerves by way of retraction or degeneration of terminal fibers during estrus. The structural loss of the terminal axon apparently is preceded by depletion of catecholamine-synthesizing enzyme.     

Spatial and nonspatial learning across the rat estrous cycle.

Recent evidence has demonstrated that there are fluctuations in both the anatomy and physiology of the hippocampus across the estrous cycle of the female rat. In the present study we examined the behavioral implications of these changes by testing females on either a hippocampal or nonhippocampal version of the Morris water maze during the various phases of the estrous cycle. Males were also tested on these tasks. Although there was little variance on the nonhippocampal cue task, females in proestrus performed significantly better than those in estrus. Optimal female performance on the spatial version of the task occurred during the phase of estrus, whereas the least efficient performance occurred during proestrus. These results do not support the traditional view that hippocampal long-term potentiation is positively correlated with spatial learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Plasma and urinary catecholamines during the human ovulatory cycle

We measured plasma catecholamine concentrations and urinary catecholamine excretion during the ovulatory cycle in six healthy women. Plasma norepinephrine was consistently at its lowest during the follicular phase of the cycle. Plasma norepinephrine began to increase about 2 days before ovulation and continued to increase after ovulation, so that the average luteal phase NE concentration was significantly higher than the average follicular phase concentration (217 versus 143 pg/ml, p less than 0.001). Urinary norepinephrine excretion showed a similar but attenuated pattern. The results suggest that sympathetic neural activity changes with the phase of the ovulatory cycle. Cyclic patterning of plasma norepinephrine is one of many factors which should be considered in the design and analysis of studies which use plasma norepinephrine as an indicator of sympathetic neural activity in human disease states.     

Influence of the estrous cycle on the norepinephrine-induced contraction of rat aorta: relationship to vascular prostanoids biosynthesis

Since ovarian sex steroids (estradiol and progesterone) may affect both blood pressure and prostanoids synthesis, and because prostaglandin-E2 (PGE2) and prostacyclin (PGI2) can modulate the vascular action of pressor hormones, we investigated the vascular reactivity to norepinephrine during the estrous cycle of the rat. In addition, we determined the vascular biosynthesis of PGE2 and 6-keto-PGF1 alpha (the stable metabolite of PGI2) at different stages of the estrous cycle. Cumulative dose-response curves were obtained by a stepwise increase in the concentration of norepinephrine. The contraction of thoracic aortic rings induced by norepinephrine did not change significantly between estrus, metestrus and diestrus. However, aortic rings obtained on proestrus showed a significant reduction in the maximal contraction (Emax) induced by norepinephrine (p < 0.001). In addition, we found significant increases in vascular synthesis of PGE2 and PGI2 on proestrus (p < 0.001). These results indicate that vascular reactivity and vascular prostanoids synthesis are influenced by the hormonal changes occurring during the estrous cycle of normal female rats. It is possible that prostanoids generated locally may play an important role in the regulation of vasomotor tone in the systemic vascular bed throughout the estrous cycle.     

The estrous cycle and estrogen modulate stress-induced analgesia.

In this article we investigate the impact of estrous cycle, ovariectomy, and estrogen replacement on both opioid and nonopioid stress-induced analgesia. Stage of estrous strongly influenced analgesia. Diestrus females exhibited the typical male pattern produced by the analgesia inducing procedures used—strong nonopioid analgesia following 10–20 tailshocks, and strong opioid analgesia following 80–200 taskshocks. In these experiments the nonopioid analgesia was slightly attenuated during estrus, but the opioid analgesia was markedly reduced. The role of estrogen in producing these changes was studied with estrogen replacement in ovariectomized subjects. Ovariectomy only slightly altered nonopioid analgesia but eliminated opioid analgesia, which suggests that some estrogen might be necessary to maintain the integrity of the system(s) underlying opioid analgesia. Estrogen administration restored opioid analgesia, but further estrogen suppressed opioid analgesia, duplicating the estrus pattern. It did not suppress nonopioid analgesia. Opioid analgesia was enhanced 102 hr after estrogen replacement, thus duplicating the diestrus pattern. Estrogen thus appears to be responsible for the impact of estrous cycle on opioid but not on nonopioid analgesia. These results suggest that ovarian hormones may modulate the impact of stressors on endogenous pain inhibition and other stress-responsive systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electric activity of the rat myometrium in vivo during the estrous cycle

Electric activity of the uterus was recorded by 6 chronically implanted wire electrodes in 17 unrestrained 5-day cycling rats. Results obtained during 196 h of recording revealed consistent changes in frequency, amplitude, temporal pattern and in direction and distance of propagation of electric activity. In estrus, bursts were short and of variable amplitude and frequency, while in metestrus bursts had high amplitude, longer duration and regular frequency. The activity decreased from metestrus to the first diestrous day and still more to the second diestrous day. In diestrus and proestrus long bursts appeared once to twice within an hour. In proestrus the morning level of activity was still low, but high at night, when it resembled the activity in estrus. Electric activity spread in both directions but with a higher frequency in the cervical direction in all phases of the cycle. Cervical electric activity appeared in synchrony with that of the uterine body and did not differ from it in type.     

Effects of oxytocin on in vitro ovarian contractility during the estrous cycle of the rat

Necrotizing skin lesions developed in a man with chronic ulcerative colitis. No evidence of intrinsic disease of medium or small-sized vessels was found. A circulating cryofibrinogen was thought to be responsible for in situ thrombosis leading to skin infarctions. Sodium warfarin in a daily dose of 2.5 to 5 mg appears to have thwarted progression of developing lesions and the occurrence of new ones.     

Reproductive hormonal responses to ergotamine and ergonovine in cows during the luteal phase of the estrous cycle

We report the abnormal albumin in members of a Thai family that presented with high serum total T3 but not T4 when measured by radioimmunoassay. In contrast, total T3 values were very low when measured by ELISA and chemiluminescence. The subjects have no goiter, and clinically euthyroid. Their serum free T4, free T3, and TSH were normal. Spiking of T3 to affected serum showed good recovery by radioimmunoassay, but very poor recovery by ELISA and by chemiluminescence. The immunoprecipitation with labeled T3 bound to albumin showed high percent precipitation in affected serum. T3-binding studies showed that the association constant of serum albumin in affected subjects was 1.5 x 10(6) M-1 or 40-fold that of unaffected relatives of 3.9 x 10(4) M-1. In contrast, the Ka of HSA for T4 in an affected subject was only 1.5-fold that of a normal. Albumin complementary DNA from leukocytes of affected member was amplified and sequenced. We found the second nucleotide of normal codon 66 (CTT), a thymine, was substituted by a cytosine (CCT), resulting in the replacement of the normal leucine by proline. This is the first report of variant albumin causing familial dysalbuminemic hypertriiodothyroninemia.     

Natural estrous cycle in normal and diabetic bitches in relation to glucose and insulin tests

The influence of spontaneous "sex seasons" on blood sugar (BS) and serum insulin levels was studied in bitches with natural diabetes mellitus (DM) and normal controls, in the basal condition and during glucose and insulin tests, was studied. DM increased basal BS, reduced glucose tolerance, distribution space (DS) and clearance from blood, and induced resistance to insulin hypoglycemic action. In normals occurrence of "seasons", inconsistently modified basal BS, increased glucose tolerance and DS; during estrogenic phase (EP), these variables were above those during luteal phase (LP). In diabetics at LP, BS found in lasting condition and during glucose test were higher than in diabetic bitches at EP (respective values at anestrous (A) in between) and glucose DS was smaller. Rate of glucose clearance from blood remained unaffected by "seasons" in both dog groups. Basal serum IRI was not modified by DM or "seasons". In normals, serum IRI response to glucose load was nonsignificant during A and increased during the "seasons"; either insulin DS or the rate of insulin clearance from blood stream remained unchanged under the circumstances, the increase being mediated by insulin secretion. During EP, the increase was particularly intense and mean insulinogenic index (MII) rose. During LP, MII returned to A value, whereby diabetic states might be manifest. Serum IRI profiles during insulin test were not modified by "seasons" in normal bitches; such response in diabetic bitches was intense during A, then decreased (EP) or was later abolished (LP). Either in normal or diabetic bitches, the sensitivity to exogenous insulin hypoglycemic action remained unchanged in spite of "seasons". In diabetic bitches at A, serum IRI after glucose challenge peaked higher than in respective normal controls (insulin clearance and insulin DS were similar): they exhibited relative insulin shortage and resistance to insulin hypoglycemic action partly compensated by promoted insulin secretion. Along with "season", abolished serum IRI response to glucose load in diabetics was observed. During EP, extrapancreatic factors regulating serum IRI concentration and MII did not change in respect to A, whereby abolishment appears mediated by depressed insulin secretion. During LP, insulin antagonism in conjunction with 1) absolute insulin deficiency and 2) intense decrease in MII appears as a powerful factor exposing diabetic bitches to a severe or fatal derangement in diabetic disease.     

Cytosolic estrogen receptor concentrations in the lumbosacral spinal cord fluctuate during the estrous cycle

Estrogen responsive neurons have been anatomically identified with autoradiographic and immunohistochemical techniques and their distribution mapped in the lumbosacral spinal cord of female rats. Such neurons contain estrogen receptors (ERs). The present study was undertaken to: 1) quantify cytosolic estrogen receptor (ER) concentrations in the lumbosacral spinal cord and 2) determine if there is a relationship between cytosolic ER concentrations and fluctuations in serum estradiol (SE2) levels during the estrous cycle. Lumbosacral spinal segments were removed from intact cycling rats during the morning of proestrus, the afternoon of proestrus, and the morning of estrus, metestrus and diestrus. Trunk blood was collected at euthanasia and SE2 levels were determined using radioimmunoassay. Cytosolic ER concentrations were measured using a dextran-charcoal coated tube method. Concentrations of cytosolic ERs were low during estrus and metestrus, increased during diestrus with maximum concentrations during the afternoon of proestrus. These changes in ER concentrations paralleled SE2 levels measured in intact cycling animals; i.e., during estrus SE2 levels were low, but began to rise during metestrus, diestrus, and during the morning of proestrus with a maximum peak increase during the afternoon of proestrus. These data indicate there are fluctuations of cytosolic ER concentrations during the estrous cycle and that these changes coincide with changing SE2 concentrations suggesting that ER content is influenced by SE2.     

The effects of 17 alpha-methyltestosterone, methandrostenolone, and nandrolone decanoate on the rat estrous cycle

In making clinical judgements, it is argued that midwives use 'shortcuts' or heuristics based on estimated probabilities to simplify the decision-making task. Midwives (n = 30) were given simulated patient assessment situations of high and low complexity and were required to think aloud. Analysis of verbal protocols showed that subjective probability judgements (heuristics) were used more frequently in the high than low complexity case and predominated in the last quarter of the assessment period for the high complexity case. 'Representativeness' was identified more frequently in the high than in the low case, but was the dominant heuristic in both. Reports completed after each simulation suggest that heuristics based on memory for particular conditions affect decisions. It is concluded that midwives use heuristics, derived mainly from their clinical experiences, in an attempt to save cognitive effort and to facilitate reasonably accurate decisions in the decision-making process.     

Astrocyte progression from G1 to S phase of the cell cycle depends upon multiple protein interaction

The proliferation of cultured astrocytes is positively and negatively regulated, respectively, by the endogenous neuropeptides, endothelin-3 (ET-3) and atrial natriuretic peptide (ANP). Here, we determined the important steps for the modulation by ET and ANP of G1 to S phase cell cycle progression. ET-3 stimulated an increased number of fetal rat diencephalic astrocytes to progress through G1/S, and this was blocked significantly by ANP. ET augmented the gene expression and/or protein production of D-type, A and E cyclins, whereas ANP inhibited these events significantly. ET also stimulated the activation of the cyclin-dependent kinases Cdk2, Cdk4, and Cdk6, directed against the retinoblastoma protein pRb, and this was inhibited by as much as 80% by ANP. As an additional mechanism of cell cycle restraint, ANP stimulated the production of multiple cyclin-dependent kinase inhibitory (CKI) proteins, including p16, p27, and p57. This was critical because antisense oligonucleotides to each CKI reversed ANP-induced inhibition of ET-stimulated DNA synthesis by as much as 85%. CKI antisense oligonucleotides also reversed the ANP inhibition of Cdk phosphorylation of pRb. In turn, ET inhibited ANP-stimulated production of the CKIs, thereby promoting cell cycle progression. Specific and changing associations of the CKI with Cdk2 and Cdk4 were stimulated by ANP and inhibited by ET. Our findings identify several mechanisms by which endogenous modulators of astrocyte proliferation can control the G1-S progression and indicate that multiple CKIs are necessary to restrain cell cycle progression in these cells.     

The role of pheromones in the regulation of estrous cycle duration in the guinea pig

A decrease in estrous cycle duration, due to shortening of the period of vaginal closure (VC), has been observed in female guinea pigs exposed to the odor of urine from males of the same species. VC shortening was also observed in females exposed to the odor of female urine collected during the period of vaginal opening (VO). No alteration in VC duration occurred, however, in females exposed to urine collected in the 1st 7 days of VC. Also VC shortening did not occur in bulbectomized females exposed to the odor of male urine. Therefore, it was concluded that guinea pig urine, when highly concentrated, contains pheromones capable of shortening estrous cycle VC.     

Patterns of follicular development during the estrous cycle in monovular Merino del Paris ewes

Growth and regression of ovarian follicles with antral diameters > or = 2 mm were characterized during 15 estrous cycles by daily transrectal ultrasonography (7.5 MHz probe) in 9 ewes of Merino del Pais, a consistently monovular Spanish breed. Mean interovulatory interval was 17.5 +/- 0.5 days and ovulation rate was 1 in all ewes; of 60 to 116 follicles, > or = 2 mm observed during the entire estrous cycle, 13.0 +/- 1.2 reached a maximum diameter > or = 4 mm and 7.9 +/- 0.6 different follicles became the largest follicle in the animal at some point during the cycle. An average of 4.5 new follicles per ewe were detected each day, with no significant effect of day of cycle. Appearance of new follicles that grew to > or = 4 mm tended to differ during the first 8 days of the cycle, being highest on day 3 and lowest on day 6 (P < 0.10), but did not vary significantly during the last 6 days. Growth of new follicles from the day of detection to the next day differed between, but not within, periods, averaging 1.4 +/- 0.3 mm of the first 8 days of the cycle and 1.8 +/- 0.5 mm from day -6 through -1 (P < 0.05). Total number of follicles > or = 2 mm per ovary on days 1 through 8 varied with the interaction of ovary by day, being more variable in the non-CL ovary. During the last 7 days, a linear decline in total follicles was coupled with a linear increase in number of large follicles (P < 0.05). Differences in the size between the largest and second largest follicles were greater on days 5 through 8 than on days 1 through 4, did not differ with day of cycle on days -6 through -1, then increased on the last day from 1.5 mm to 2.9 mm (P < 0.001). In conclusion, the monovular Merino del Pais ewe showed a more rapid growth and turnover of ovarian follicles than other breeds studied, but identified 3-mm follicles did not emerge in other than a random distribution. There was little evidence of dominance until the ovulatory follicle had been identified.     

Allopregnanolone concentration in hippocampus of prepubertal rats and female rats throughout estrous cycle

Hippocampus plays an important role in cognition, neuroendocrine function and sexual behaviour. Changes of hippocampal neuropeptide and neurotransmitter concentrations are associated to behavioural changes occurring throughout reproductive life. The present study focused the attention on the presence of a neurosteroid, 5 alpha-pregnan-3 alpha-ol-20-one (termed allopregnanolone) in hippocampus. In particular, hippocampal allopregnanolone concentration in male and female prepubertal rats and in female rats throughout estrous cycle were evaluated. Hippocampal extracts were eluted on high pressure liquid chromatography and allopregnanolone concentration was measured by radioimmunoassay. Prepubertal male and female rats (15 days old) showed highest values which significantly decreased with advancing age (25 and 60 days) (p < 0.01); the lowest hippocampal concentration of allopregnanolone was found in adult rats. Female rats on proestrus morning and afternoon showed an hippocampal allopregnanolone concentration significantly higher than on diestrus or on estrus (p < 0.01), while rats on estrus showed hippocampal allopregnanolone concentration significantly lower than during other days of estrus cycle (p < 0.01). These data indicate differences in hippocampal concentration of allopregnanolone between prepubertal and adult rats and throughout estrous cycle in female rats. This finding suggest a putative role of neurosteroids in the modulation of behavioral changes occurring throughout reproductive life.