Members of opposite sex mutually regulate gonadal recrudescence in the lizard Calotes versicolor Agamidae)

Adult males and females of the seasonally breeding lizardCalotes versicolor were subjected to various social situations under semi-natural conditions to explain the role of socio-sexual factors in gonadal recrudescence. They were grouped as: (i) males and females, (ii) males and females separated by a wire mesh, (iii) same sex groups of males or females, (iv) castrated males with intact females and (v) ovariectomized (OvX) females with intact males from postbreeding to breeding phase. Specimens collected from the wild during breeding season served as the control group. Plasma sex steroid levels (testosterone in male and 17β-estradiol in female), spermatogenetic activity and vitellogenesis were the criteria to judge gonadal recrudescence. In intact males and females that were kept together, gonadal recrudescence and plasma sex steroids levels were comparable to those in wild-caught individuals. Gonadal recrudescence was at its least in all male and all female groups, and plasma sex steroids were at basal levels. Association with OvX females initiated testicular recrudescence but spermatogenetic activity progressed only up to the spermatid stage while males separated from females by wire mesh showed spermatogenetic activity for a shorter period. Females grouped with castrated males and those separated from males by wire mesh produced vitellogenic follicles. However, the total number and diameter of vitellogenic follicles, and plasma estradiol levels were lower than in the females grouped with intact males. The findings indicate that association with members of the opposite sex with progressively rising titers of sex steroids is crucial in both initiating and sustaining gonadal recrudescence in the lizard. Thus, members of the opposite sex mutually regulate gonadal recrudescence in theC. versicolor.     

Evidence for extended action of gonadal hormones on the organization of sexually dimorphic behavior and morphology in gray short-tailed opossums (Monodelphis domestica)

Male and female gray short-tailed opossums were gonadectomized (GDX), or treated with the estrogen receptor antagonist tamoxifen citrate (TX), or corn oil (OIL) (control) during the 5th postnatal week, a time period equivalent to the 3rd postnatal week in rats and associated with high levels of circulating gonadal hormones and neural aromatase activity in this marsupial species. In adulthood following gonadectomy (for animals not previously gonadectomized) and replacement therapy with estradiol or testosterone, GDX males showed less male-typical scent marking and had shorter phalluses than OIL and TX males. Following replacement therapy with estradiol, GDX females were more likely to fight with and less likely to mate with stimulus males than TX females; OIL females were intermediate in these measures. Along with previous findings, these results suggest that gonadal hormones act over an extended postnatal period to organize sexually dimorphic behavior and morphology in male gray opossums and may have some effect on the organization of aggressive behavior in females of this species.     

Differential effects of the perinatal steroid environment on three sexually dimorphic parameters of the rat brain

Gonadectomy of male rats was performed at 0, 6-7 (6h), 12-13 (12h), or 24 h postnatally in order to examine the influence of testosterone exposure on sexual differentiation of the brain. The indices examined were: the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) titers following estradiol benzoate (EB) and progesterone (P) administration. Control animals were sham-operated at 0 h and gonadectomized at 29 days of age (sham). A decrease in the percentage of males with elevated plasma LH levels following P was found with increasing delay before gonadectomy. Significant (P less than 0.001) differences existed in the amplitude of plasma LH titers 5 h following P administration between sham, 0 h, and 6 h groups. Follicle-stimulating hormone was also elevated in all neonatally gonadectomized male groups following P administration, but there was no difference between the groups. Volume of the SDN-POA was significantly (P less than 0.001) smaller in all gonadectomized males when compared to that of sham-operated males, but no differences existed between males gonadectomized at the different hours postpartum. In female rats gonadectomized at 0 h (F0h), LH levels were elevated 5 h following P, but only to a magnitude of 36% of that of sham-operated controls (P less than 0.001). Volume of the SDN-POA of the F0h group was significantly reduced (P less than 0.05) when compared to that of sham females. Thus, in males, the presence of the tests prenatally may be responsible for the initiation of masculinization of LH release mechanisms and the SDN-POA, but both require further androgen exposure for their completion. In addition, the LH and FSH regulating systems show a differential sensitivity to the steroid hormone environment during development that shapes the animal's response to steroid as an adult.     

The influence of sex and gonadectomy on the growth hormone and corticosterone response to hexarelin in the rat

The present study is designed to investigate the role of sex and gonadal status in the growth hormone (GH) and corticosterone response to hexarelin (HEXA), a GH-releasing peptide, which also causes a stimulatory action on the hypothalamic-pituitary-adrenal (HPA) axis. HEXA (80 microg/Kg) was administered intracarotid to anesthetized intact or gonadectomized male (ORC) and female (OVX) middle-aged rats. The GH stimulatory response to HEXA was gender-related since the GH increase was significantly (p < 0.001) higher in intact males (area under the curve, AUC= 12560 +/- 1784 ng/ml.45 min) than in females (AUC= 4628 +/- 257 ng/ml.45 min). This sex difference does not depend on circulating gonadal steroids since it persists in ORC (AUC = 11980 +/- 1136 ng/ml.45 min) and OVX (AUC = 5539 +/- 614 ng/ml.45 min) rats. The different effects of HEXA on corticosterone secretion detected in male and female rats are probably dependent on the prevailing activity of the HPA axis. In fact, in male rats that have low basal corticosterone levels, HEXA caused an increase in corticosterone secretion, which was significantly (p< 0.05) higher in ORC than in intact rats. The increase in corticosterone secretion by HEXA both in intact and OVX females was delayed, probably due to the elevated initial corticosterone levels, which could have activated the glucocorticoid negative feedback. We suggest that gender-specific patterns in the regulation of the hypothalamus-pituitary function could be responsible for the GH and corticosterone sexually differentiated responses to HEXA.     

Effects of gonadectomy and sex hormones on the levels of noradrenaline and dopamine in rat hypothalamus

The levels of noradrenaline and dopamine were determined in the homogenates of the hypothalamus of rats of either sex. The determinations were done in intact rats, after sham gonadectomy, 6 and 9 weeks after gonadectomy, and in gonadectomized rats receiving 6 weeks after gonadectomy one dose of oestradiol cypionate (females) or testosterone cypionate (males). Catecholamines were determined fluorimetrically. The changes of the determined catecholamines differed in the hypothalamic homogenates in males and females after gonadectomy. Following orchidectomy the noradrenaline level rose, while after ovariectomy the level of this catecholamine decreased. Contrary to this, in ovariectomized rats the dopamine level was significantly raised after the operation. This change was reversible as observed after administration of oestradiol cypionate. Orchidectomy and testosterone cypionate injection had no effect on the dopamine level in the hypothalamus. The role of these catecholamines in the processes connected with the regulation of the hypothalamus-hypophysis-gonad axis is discussed.     

Prenatal testosterone exposure leads to hypertension that is gonadal hormone-dependent in adult rat male and female offspring

Prenatal testosterone exposure impacts postnatal reproductive and endocrine function, leading to alterations in sex steroid levels. Because gonadal steroids are key regulators of cardiovascular function, it is possible that alteration in sex steroid hormones may contribute to development of hypertension in prenatally testosterone-exposed adults. The objectives of this study were to evaluate whether prenatal testosterone exposure leads to development of hypertension in adult males and females and to assess the influence of gonadal hormones on arterial pressure in these animals. Offspring of pregnant rats treated with testosterone propionate or its vehicle (controls) were examined. Subsets of male and female offspring were gonadectomized at 7 wk of age, and some offspring from age 7 to 24 wk received hormone replacement, while others did not. Testosterone exposure during prenatal life significantly increased arterial pressure in both male and female adult offspring; however, the effect was greater in males. Prenatal androgen-exposed males and females had more circulating testosterone during adult life, with no change in estradiol levels. Gonadectomy prevented hyperandrogenism and also reversed hypertension in these rats. Testosterone replacement in orchiectomized males restored hypertension, while estradiol replacement in ovariectomized females was without effect. Steroidal changes were associated with defective expression of gonadal steroidogenic genes, with Star, Sf1, and Hsd17b1 upregulation in testes. In ovaries, Star and Cyp11a1 genes were upregulated, while Cyp19 was downregulated. This study showed that prenatal testosterone exposure led to development of gonad-dependent hypertension during adult life. Defective steroidogenesis may contribute in part to the observed steroidal changes.     

Mechanisms of 17beta-estradiol on the production of ET-1 in ovariectomized rats

In order to clarify the mechanism underlying the possible preventive effect of estrogen on atherogenesis, we investigated the role of 17beta-estradiol (E2) in the regulation of endothelin-1 (ET-1) production in ovariectomized rats, which may contribute to atherogenesis. Female Spragure-Dawly rats were randomly divided into three groups: sham-operated group (sham), ovariectomized group (OVX) and 17beta-estradiol replacement group (OVX + E2, 20 microg(-1).kg.d(-1),s.c.). 4 weeks after operation, the plasma concentration of ET-1, clearance of ET-1, functional ECE activity and preproET-1 mRNA expression in aorta were measured. Concentration of plasma ET-1 change from 107.8 +/- 18.3 pg/ml (sham) and 135.5 +/- 27.6 pg/ml (OVX + E2) to 190.7 +/- 25.5 pg/ml (OVX ) (n = 8, p < 0.05). There was no significant difference in the clearance of 125IET-1 among three groups (p > 0.05). Functional ECE activity was increased in OVX group in comparison to that in sham group (p < 0.05). The OVX increased the preproET-1 mRNA expression in sham, whereas treatment with estrogen reversed these changes (p < 0.05). The present study have shown that estrogen down-regulates plasma ET-1 levels by inhibiting the preproET-1 mRNA expression and functional ECE activity. Clearance of ET-1 was not affected. Inhibition of ET-1 production mediated by modulating ECE activity may be one of the novel mechanisms of the protective of estrogens on the cardiovascular system.     

Prolonged Ethanol Ingestion Increases Renal AQP2 and AQP3 Expression in Adult Ratsand in Their Offspring

This study evaluates the effect of prolonged ethanol ingestion on the renal ability to concentrate urine. Suckling Wistar rats born to mothers given ethanol before and during gestation and suckling periods (ethanol-exposed offspring) were used and the results were compared with those obtained from offspring of dams given diets containing no ethanol. Comparisons were also made between progenitors with or without prolonged ethanol ingestion. Body and kidney weights; arginine-vasopressin (AVP) and aldosterone plasma levels; plasma, urine and renal papillary osmolality; urine outflow; kidney AQP2, AQP3 and AQP4 expression and diencephalon AVP mRNA expression were determined. As compared with control offspring, the ethanol-exposed offspring present i) lower body and kidney weights; ii) lower urine outflow; iii) higher renal AQP2 and AQP3 mRNA; iv) higher renal AQP2 protein content and v) higher urine and renal papillary osmolality. These changes were also observed in the ethanol-treated progenitors, although they were of smaller magnitude. Plasma osmolality, renal AQP4 mRNA, AVP plasma levels and diencephalon AVP mRNA expression were not affected by the ethanol treatment. Plasma levels of aldosterone were only significantly increased in the ethanol-exposed suckling rats. It is concluded that maternal ethanol ingestion before and during gestation and suckling periods affects the renal function of the offspring, up-regulating renal AQP2 expression by an AVP-independent mechanism. Ethanol-treated progenitors manifest similar renal changes, although of lesser magnitude than the offspring.     

Protective effects of estrogen on gender-specific development of diet-induced hypertension.

Dietary and humoral factors are thought to be involved in the development of hypertension. This study investigated the interaction between diet and gonadal hormone status in the development and reversibility of hypertension. Normal male and female and ovariectomized (OVX) female Fischer rats were placed on either a high-fat (primarily saturated), refined carbohydrate (sucrose) (HFS) or a low-fat, complex carbohydrate (LFCC) diet at 2 mo of age, and body weight and systolic blood pressure (BP) were measured. Male and OVX female rats were initially on the diets for 7 mo, whereas normal female rats were on the diets for 2 yr. After this initial phase, a group of rats from each of the normal HFS groups were converted to the LFCC diet for a period of 1 mo (males) and 2 mo (females). The OVX females were subcutaneously implanted with a 0.5-mg estradiol (E2) pellet for 1 mo. A significant rise in arterial BP occurred within 12 mo in female and only 2 mo in male rats on the HFS diet, exceeding 140 mmHg after 24 and 7 mo, respectively. Conversion from the HFS to the LFCC diet led to a normalization of BP in both female and male rats. HFS diet-induced hypertension was accelerated by OVX in female rats, approaching the pattern seen in male rats. The effect of OVX was completely reversed by E2 replacement. BP did not significantly change in any of the LFCC groups at any time point, and E2 replacement had no effect on BP in the OVX LFCC group. All HFS groups had significantly greater body weight, with differences occurring sooner in the male and OVX rats compared with the female rats. Diet modification resulted in a partial but significant reduction of body weight, but E2 replacement did not. These results demonstrate that long-term consumption of HFS diet induces hypertension in both genders and is reversible by diet modification. Hypertension is significantly delayed in females with functional ovaries. This protection is lost by OVX and restored by estrogen replacement. Thus hormone status contributes to the delayed onset of diet-induced hypertension in females compared with males.     

Influence of gonadal hormones on odours emitted by male meadow voles (Microtus pennsylvanicus).

Free-living male meadow voles (Microtus pennsylvanicus) emit odours that are attractive to females at the beginning, but not at the end, of the breeding season. The effect of gonadal hormones on female-attractant cues was examined in males born and reared in long (14 h light day-1) and short (10 h light day-1) photoperiods that simulate daylengths in the breeding and nonbreeding seasons, respectively. Gonadectomy affected the attractant properties of odours emitted by long photoperiod, but not short photoperiod, males. Long photoperiod females preferred odours of intact rather than those of gonadectomized long photoperiod males, and odours of gonadectomized long photoperiod males rather than those of intact short photoperiod males. Females did not show a preference between the odours of intact and castrated short photoperiod males. Gonadal hormone replacement in males affected female responses to the odours emitted by long photoperiod, but not short photoperiod, gonadectomized males. Long photoperiod females did not display a preference between odours of intact long photoperiod males and gonadectomized long photoperiod males treated with testosterone or oestradiol. We conclude that in spring and summer gonadal hormones increase attractiveness of male odours; this effect may require aromatization of testosterone to oestradiol. Substrates that control attractiveness of odour cues in male voles appear to be unresponsive to androgens during the nonbreeding season.     

Pharmacological blockage of serotonin biosynthesis and circadian changes in oxaliplatin toxicity in rats

This study investigates if the serotoninergic system plays a role in chronotoxic effects of the anticancer agent oxaliplatin (l-OHP). Four groups of female rats (120 in total) synchronized with light-dark (12 h:12 h) were treated with: (i) saline, (ii) para-chlorophenylalanine (pCPA, an inhibitor of serotonin biosynthesis: 300 mg/kg/d, i.p. for two consecutive days), (iii) l-OHP (23 mg/kg, i.v.) at three different dosing times, or (iv) both pCPA and l-OHP. The results show pCPA (ii) obliterates the circadian rhythm in plasma ACTH but not in corticosterone or leukocytes, and (iii) l-OHP exerts circadian time-dependent toxic effects (body weight loss, leukopenia, and intestinal lesions) with greatest toxicity coinciding with treatment at the end of the nocturnal activity span (P < 0.05). In rats whose serotonin biosynthesis was blocked (iv), the circadian rhythms in the toxic effects of l-OHP and in ACTH were obliterated, while the rhythms in corticosterone and leukocytes persisted.     

Inhibition of Estrogen-Induced Sexual Receptivity by Androgens: Role of the Androgen Receptor

Both naturally occurring and synthetic androgens have been shown to inhibit estrogen-induced sexual receptivity when administered to ovariectomized (OVX) rats. The mechanisms by which androgens exert these effects, however, remain unclear. Experiments were conducted to determine the role of the androgen receptor in the inhibition of estrogen-induced sexual receptivity in OVX rats by using flutamide, an androgen receptor antagonist. In each experiment, OVX Long–Evans rats received 6 consecutive days of estradiol benzoate (EB; 2.0 μg/day) followed by 15 days of EB concurrent with flutamide (10.0 mg/kg; twice daily) or the vehicle and one of the following androgens or the vehicle: dihydrotestosterone propionate (7.5 mg/kg), 3α-androstanediol (3.75 mg/kg), 17α-methyltestosterone (7.5 mg/kg), stanozolol (7.5 mg/kg), or nandrolone decanoate (7.5 mg/kg). On Day 15, all female rats received progesterone (P; 1.0 mg/rat) 4 h before testing. Tests for sexual receptivity were conducted on Days 3, 6, 14, and 15 of androgen/flutamide treatment. Each androgen inhibited sexual receptivity as expected, and concurrent treatment with flutamide reversed the inhibitory effects of all androgens on sexual receptivity on all test days. High levels of sexual receptivity were displayed in response to P on Day 15, regardless of experimental treatment. These results suggest that naturally occurring and synthetic androgens act at the androgen receptor to inhibit estrogen-induced sexual receptivity in OVX rats.     

Ovariectomy worsens secondary hyperparathyroidism in mature rats during low-Ca diet

Estrogen deficiency impairs intestinal Ca absorption and induces bone loss, but its effects on the vitamin D-endocrine system are unclear. In the present study, calciotropic hormones levels, renal vitamin D metabolism, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-dependent intestinal calcium absorption, and bone properties in 3-mo-old sham-operated (sham) or ovariectomized (OVX) rats fed either a normal-Ca (NCD; 0.6% Ca, 0.65% P) or a low-Ca (LCD; 0.1% Ca, 0.65% P) diet for 2 wk were determined. LCD increased serum 1,25(OH)2D3 levels in both sham and OVX rats. Serum parathyroid hormone [PTH(1-84)] levels were highest in OVX rats fed LCD. Renal 25-hydroxyvitamin D1alpha-hydroxylase (1-OHase) protein expression was induced in both sham and OVX rats during LCD, while renal 1-OHase mRNA expression was highest in OVX rats fed LCD. Renal vitamin D receptor (VDR) and mRNA expressions in rats were induced by ovariectomy in rats fed NCD but suppressed by ovariectomy in rats fed LCD. The induction of intestinal calcium transporter-1 and calbindin-D9k mRNA expressions by LCD were not altered by ovariectomy. As expected, bone Ca content, cancellous bone mineral density, and bone strength index in proximal metaphysis of rat tibia were reduced by both ovariectomy and LCD (P<0.05) as analyzed by two-way ANOVA. Taken together, the data demonstrate that ovariectomy alters the responses of circulating PTH levels, renal 1-OHase mRNA expression, and renal VDR expression to LCD. These results suggest that estrogen is necessary for the full adaptive response to LCD mediated by both PTH and 1,25(OH)2D3.     

Hormonal changes affect the bone and bone marrow cells in a rat model

In this study, we used a rat model to investigate the effects of gonad hormones and replacement therapy on bone structure and the immune system. In the first phase of the study, 3- and 11-month-old F344 rats underwent ovariectomy (OVX) or were sham operated. Three months later, severe osteopenia was histologically observed in OVX rats of both age groups. The changes in the bone marrow structure of OVX rats included deterioration of cancellous bone that was associated with a remarkable increase of adipocyte cells. Furthermore, differential analyses for the expression of cell surface antigens by lymph-myeloid cells was studied using flow cytometry (FACS). The number of myeloid cells expressing ED-9(+) or CD-44(+) was similar in both age groups, and unaffected by OVX. However, an augmentation of T-lymphoid cells expressing CD4(+), CD5(+), or both, were observed with age, as well as after OVX. In the second phase of the study, 11-month-old rats were divided into five experimental groups: sham-operated, OVX, and OVX treated with sustained-release pellets of 17beta-estradiol (OVX-E), progesterone (OVX-P), or both (OVX-E/P). Hormone replacement therapy maintained low physiological levels, and rats were tested 12 weeks after treatment initiation. Administration of 17beta-E, with or without the addition of progesterone, prevented the rise of T lymphoid cells observed in OVX rats, whereas progesterone alone had no effect. In agreement with findings from the first phase, neither OVX nor replacement therapy affected the myeloid cells expression of ED-9 or CD-44. In summary, the cellular changes in the bone marrow of OVX rats were associated with an increase in adipocytes that was correlated with bone atrophy. An augmentation of T-lymphopoiesis was noted with increase in age or after OVX. This increase was reversed to baseline levels by 17beta-E treatment.     

Testosterone and sexual experience alter levels of plasma membrane binding sites for progesterone in the male rat brain.

Physiological levels of progesterone act in conjunction with androgens to facilitate copulatory behavior in male rats, mice, and lizards. Radiolabeled progesterone conjugated to bovine serum albumin measured specific binding sites in membrane fractions from male rats that were gonadectomized and testosterone treated, or remained gonadally intact, to determine the role of gonadal steroids on mPR binding. To determine whether behavioral experience could alter binding levels, males either remained sexually na?ve or became sexually experienced. In sexually na?ve males, the highest levels of specific binding occurred in the dorsal portions of the medial preoptic area, with only moderate levels of binding in ventral portions of the medial preoptic area and the dorsal and ventral medial hypothalamus. However, conjugated progesterone binding in these brain regions did not change as a function of testosterone or behavioral manipulations. In contrast, the amygdala responded to behavioral experience with significantly (4-fold) increased binding in gonadectomized, T-treated males with sexual experience. These data indicate that the neuronal plasticity for membrane-associated progesterone binding is regionally specific, being regulated by sexual experience following the reinstatement of testosterone levels, thus suggesting a functional role for plasma membrane activity of progesterone in male rat reproduction.     

The impact of nandrolone decanoate administration on ovarian and uterine tissues in rat: Luteinizing hormone profile,histopathological and morphometric assessment

The study had been conducted to evaluate the effects of nandrolone decanoate (abused repeated doses) on female rat’s ovary and uterus during administration and withdrawal. The study included 18 rats that were divided into control group (n = 6) and treated group (n = 12). The treated group was injected intramuscular (IM) with nandrolone decanoate (7 mg/kg body weight) for three consecutive days, for two weeks. The study stated that nandrolone decanoate increases the weights of body, ovary, and uterus. Moreover, it has a tendency of bringing upon modifications in the biochemical, histopathological, and morphological makeup of the female reproductive aspects. In conclusion, nandrolone decanoate has been identified as deleterious element for the female rats, and it is suggested that keen observations must be made on the human abusers to control and manage the possible pathologies.     

Interaction between nandrolone decanoate and calcitonin in bone formation markers (osteocalcin and bone specific alkaline phosphatase) and IGF-I in rats

Bone tissue has been shown to contain numerous cell-to-cell signaling peptides called growth factors. These growth factors are thought to have important regulating effects for bone remodeling, due to their potent effects on bone cell metabolism. Our investigation was intended to assess the effect of nandrolone decanoate and calcitonin treatment on biochemical markers of bone formation (bone alkaline phosphatase - osteocalcin) and insulin-like growth factor-I in rats. We studied 48 adult male rats. The animals were divided into four groups. Group (A) served as control. Animals in Group (B) were injected with 4 mg/kg/day nandrolone decanoate. Animals in Group (C) were injected with 400mU/rat/day calcitonin and Group (D) received combined therapy for seven days. Nandrolone decanoate and calcitonin have a mild but significant effect on insulin-like growth factor-I without affecting osteocalcin levels, while calcitonin alone decreases the BALP levels. The coadministration of two agents caused notable elevation on insulin-like growth factor-I, followed by a significant increase of osteocalcin and bone alkaline phosphatase.     

Influence of estradiol on micturition thresholds in the rat: involvement of the hypogastric nerve

Studies have shown that the severity of bladder hyperreflexia induced by acute bladder inflammation varies with the ovarian cycle. These results suggest that the hyperreflexia is modulated by ovarian hormones. Other studies have suggested that such modulation involves the bladder's sympathetic innervation. These hypotheses were tested by assessing the development of bladder hyperreflexia in urethane-anesthetized rats subjected to different hormonal manipulations with or without bilateral hypogastric neurectomy (HYPX). The groups included sham ovariectomy (sham OVX), ovariectomy (OVX), OVX with estradiol replacement (OVX+E), OVX+HYPX, and OVX+HYPX+E. Assessments were performed using repeated cystometrograms (CMGs) to measure micturition thresholds (MT) before and hourly for 3 h after intravesicular treatment with 50% turpentine oil (or olive oil in an OVX+E control group). In the uninflamed bladder, treatment with estradiol increased MTs in the OVX+E group compared with the OVX group. As expected, bladder inflammation induced bladder hyperreflexia in sham OVX rats (studied in estrus). This hyperreflexia was eliminated by OVX and restored by either estradiol replacement or HYPX. Combining estradiol replacement and HYPX (i.e., OVX+E+HYPX) did not increase the severity of bladder hyperreflexia compared with either manipulation alone. These results indicate that the bladder hyperreflexia that is induced by bladder inflammation requires the presence of estradiol and suggest that this hormonal modulation is exerted via the sympathetic control of the bladder, possibly via an increase of beta-adrenergic inhibitory actions on the detrusor muscle. Similar mechanisms may contribute to bladder disorders in postmenopausal women.