Estrogens and phytoestrogens: brain plasticity of sexually dimorphic brain volumes.

Sexually dimorphic brain volumes (sexually dimorphic nucleus of the preoptic area (SDN-POA) and anteroventral periventricular (AVPV) nucleus) are influenced by estrogens. Phytoestrogens, derived from plants (especially soy products), are molecules structurally and functionally similar to estradiol. The purpose of this study was to examine: the consumption of phytoestrogen (using a phytoestrogen-rich (Phyto-600) versus a phytoestrogen-free (Phyto-free)) diets from conception to adulthood (or changing the diets during adulthood) and characterizing (a) circulating plasma phytoestrogen levels, (b) testosterone levels in males, (c) sexually dimorphic brain volumes (i.e. the SDN-POA and AVPV) and (d) the presence of apoptotic cells in these brain structures in Long-Evans rats. Phyto-600 fed animals displayed total serum phytoestrogens levels 37-fold higher compared to Phyto-free values. Circulating testosterone levels were not significantly altered by the diets. Female SDN-POA volumes were not altered by the diets. Whereas, males fed a Phyto-free diet displayed decreased SDN-POA volumes compared to male Phyto-600 values. Females fed the Phyto-600 diet displayed larger AVPV volumes compared to males on the same diet or females on the Phyto-free diet. Males fed the Phyto-free diet had the largest AVPV values compared to Phyto-600 fed males. When the SDN-POA region was examined in lifelong Phyto-free fed males, apoptotic cells were present versus males fed the Phyto-600 diet and in the AVPV region the opposite results were obtained. In summary, consumption of dietary phytoestrogens (estrogen mimics) can alter hormone-sensitive hypothalamic brain volumes in rodents during adulthood.

Dietary soy phytoestrogen effects on brain structure and aromatase in Long-Evans rats.

Phytoestrogens are estrogen-like (plant-derived) molecules that protect against age-related diseases (cardiovascular disease and osteoporosis), hormone-dependent (breast and prostate) cancers and selectively bind estrogen receptors. However, little is known about the influence of phytoestrogens on brain. Using diets containing either high phytoestrogen levels, derived from soy, or very low phytoestrogens we quantified phytoestrogen concentrations of daidzein, genistein and equol in brain. We found that dietary phytoestrogens: significantly decrease body and prostate weights, do not alter brain aromatase levels and significantly change during adulthood the structure of the sexually dimorphic brain region (i.e. anteroventral periventricular nucleus; AVPV) in male, but not in female rats. Since most commercial animal diets contain significant concentrations of phytoestrogens their influence on brain structure should be considered.

Brain androgen and progesterone metabolizing enzymes: biosynthesis, distribution and function.

This review summarizes the biosynthesis, cell type-distribution and function of brain aromatase cytochrome P450 (P450aro) and 5alpha-reductase enzymes. This overview covers the impact of the steroid products of the P450aro and 5alpha-reductase enzymes in establishing sexually dimorphic brain structures, specifically the sexually dimorphic nucleus of the preoptic area (SDN) and the anteroventral periventricular nucleus (AVPV). Additionally, since metabolites of the P450aro and 5alpha-reductase enzymes are known to regulate the calcium-binding protein, calbindin (CALB), CALB is reviewed in relationship to its potential role in determining sexually dimorphic brain structures. Finally, recent reports indicate that phytoestrogens inhibit P450aro and 5alpha-reductase activities in peripheral tissue sites, therefore, the effects of phytoestrogens on brain P450aro and 5alpha-reductase are briefly considered and the impact of consuming a high vs. a low phytoestrogen diet on visual spatial memory in male and female rats is presented.

Altered sexually dimorphic nucleus of the preoptic area (SDN-POA) volume in adult Long-Evans rats by dietary soy phytoestrogens.

Naturally occurring estrogen-like molecules in plants (phytoestrogens), present via soy, in animal diets can alter morphology and physiology in rodents. Phytoestrogens have the ability to bind estrogen receptors and exert many of the biological responses evoked by physiological estrogens. This study characterized the effects of dietary phytoestrogens on the expression of body and prostate weight, circulating testosterone and estradiol levels, puberty onset, vaginal cyclicity, and volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in Long-Evans rats. Using different experimental protocols, animals were fed either a phytoestrogen-rich (Phyto-600) or a phytoestrogen-free (Phyto-free) diet. Animals fed the Phyto-600 diet displayed significantly decreased body weights (in males and females), prostate weights and delayed puberty in females compared to that of animals fed the Phyto-free diet. Circulating testosterone or estradiol levels in males or estrous cyclicity were not altered by the diets. The volume of the SDN-POA was significantly altered by a change in diet at 80 days of age where one-half of the males or females fed the Phyto-600 diet (from birth) were switched to the Phyto-free diet until 120 days of age. Males initially fed a Phyto-600 diet but changed to a Phyto-free diet had significantly smaller SDN-POA volumes compared to males fed the Phyto-600 diet (long-term). These data suggest that consumption of phytoestrogens via a soy diet, significantly: (1) decreases body and prostate weight, (2) delays puberty onset, and (3) alters SDN-POA volumes during adulthood.

Dietary soy phytoestrogens produce anxiolytic effects in the elevated plus-maze.

Naturally occurring estrogen-like molecules in plants (phytoestrogens), present via soy, in animal diets, exert many of the biological responses evoked by physiological estrogens. This study characterized the effects of dietary phytoestrogens on the expression of body weight, consummatory behavior, and anxiety (as expressed in the elevated plus-maze). Phytoestrogens produced anxiolytic effects in both male and female Long-Evans rats. Additionally, phytoestrogens decreased body weight but increased consumption of food and/or water.

Steroid hormone influence on brain calbindin-D(28K) in male prepubertal and ovariectomized rats.

Calbindin-D(28K) (CALB), a calcium-binding protein, is thought to buffer intracellular calcium levels in neurons playing several important roles during central nervous system development such as, protecting against apoptosis (programmed cell death), neurodegenerative diseases and influencing sexually dimorphic brain structures. While preliminary research indicates that calbindin levels are modulated by steroids, there has not yet been a comprehensive study to determine the role androgens, androgen metabolites and corticosterone have on CALB expression in males and throughout the estrous cycle in rats. The present study had two main components utilizing Western analysis: (1) examination of the influence of steroid hormones (testosterone, dihydrotestosterone, corticosterone, and estradiol) and aromatase and 5alpha-reductase blockers on rat brain CALB expression in frontal cortex, MBH-POA, and cerebellum of male rats in experiment 1; (2) characterization of CALB abundance in frontal cortex, MBH-POA, and cerebellum throughout the hormonally induced estrous cycle of rats in experiment 2. There were no significant alterations in CALB levels by any of the treatments in experiment 1 or experiment 2 when frontal cortical tissue was examined. In male MBH-POA samples, estradiol treatment significantly increased CALB levels compared to oil-injection and aromatase or 5alpha-reductase blockers. Additionally, DHT treatment significantly increased CALB levels vs. 5alpha-reductase blocker values. In female samples, MBH-POA CALB levels increased from diestrus through proestrus and estrus to metestrus, where metestrus values were significantly higher compared to diestrus levels. In the cerebellum, the only significant alteration in CALB levels, in males, was observed in corticosterone-treated animals where a significant decrease was seen compared to oil injection. In females, cerebellum CALB levels increased from diestrus through proestus, with a slight decrease at estrus. Thereafter, CALB levels increased during metestrus where cerebellar CALB values were significantly higher than diestrus levels. These findings suggest that steroid hormones play an important regulatory role in CALB expression in the brain (except for the frontal cortex) where it potentially influences the development/function and neuroprotective changes of neuroanatomical structures.

Dietary soy-phytoestrogens decrease testosterone levels and prostate weight without altering LH, prostate 5alpha-reductase or testicular steroidogenic acute regulatory peptide levels in adult male Sprague-Dawley rats.

Nutritional factors, especially phytoestrogens, have been extensively studied for their potential beneficial effects against hormone-dependent and age-related diseases. The present study describes the short-term effects of dietary phytoestrogens on regulatory behaviors (food/water intake, locomotor activity and body weight), prostate weight, prostate 5alpha-reductase enzyme activity, reproductive hormone levels, and testicular steroidogenic acute regulatory peptide (StAR) levels in adult Sprague-Dawley rats. Animals were fed either a phytoestrogen-rich diet containing approximately 600 microg/g isoflavones (as determined by HPLC) or a phytoestrogen-free diet. After 5 weeks of consuming these diets, plasma phytoestrogen levels were 35 times higher in animals fed the phytoestrogen-rich vs phytoestrogen-free diets. Body and prostate weights were significantly decreased in animals fed the phytoestrogen-rich diet vs the phytoestrogen-free fed animals; however, no significant change in prostate 5alpha-reductase enzyme activity was observed between the treatment groups. Locomotor activity levels were higher in the phytoestrogen-rich vs the phytoestrogen-free animals during the course of the treatment interval. Plasma testosterone and androstenedione levels were significantly lower in the animals fed the phytoestrogen-rich diet compared with animals fed the phytoestrogen-free diet. However, there were no significant differences in plasma LH or estradiol levels between the diet groups. Testicular StAR levels were not significantly different between the phytoestrogen-rich vs the phytoestrogen-free fed animals. These results indicated that consumption of dietary phytoestrogens resulting in very high plasma isoflavone levels over a relatively short period can significantly alter body and prostate weight and plasma androgen hormone levels without affecting gonadotropin or testicular StAR levels. The findings of this study identify the biological actions of phytoestrogens on male reproductive endocrinology and provide insights into the protective effects these estrogen mimics exert in male reproductive disorders such as benign prostatic hyperplasia and prostate cancer.

Effects of maternal separation during early postnatal development on male sexual behavior and female reproductive function.

The endocrine response to stress is an important homoeostatic mechanism, and the secretion of glucocorticoids from the adrenal cortex is a central feature of this response. During early postnatal development, the neonatal rat displays a reduced hypothalamic-pituitary-adrenal (HPA) response to stress. This early period has been termed the 'stress hyporesponsive period' (SHRP). Maternal separation (Sep) of neonates from their mothers during early postnatal development alters the HPA response to stress. In this study, we report the effects of Sep during the SHRP. Female rats were time mated and randomly divided into control or Sep groups before birth. The Sep litters were removed from the mothers during the dark cycle for 6 h per day from postnatal day (PND) 2 to 10. On PND 28, the pups from both groups were weighed, the anogenital distance (AGD) was measured and the animals weaned. At 40 days of age, male and female animals from both groups were tested for open-field activity. As the animals matured, vaginal opening and estrous cycles were measured in females, and males were tested for male sexual behavior at adulthood. Basal, stress, and stress recovery serum corticosterone levels were measured from control and Sep male and female animals. Open-field activity was not significantly different between control or Sep male or female animals. Sep did not affect either vaginal opening or estrous cycles in female animals. Corticosterone secretion in response to stress was similar in control and Sep males and females; however, the recovery levels were significantly higher in Sep females than in Sep males or female control values. In male sexual behavior tests, Sep males had significantly longer mount latencies (time to the first mount), longer intromission latencies (time to the first intromission) and a significant reduction in the percent of animals ejaculating versus control values (controls 84 and Sep 50%). Therefore, Sep males as adults displayed altered reproductive behavior, whereas their stress recovery levels of corticosterone returned to near basal levels in a similar fashion to that observed for control non-handled males. In contrast, females displayed normal reproductive physiology, while their recovery levels of corticosterone remained high, unlike that observed with control females. Thus, significant gender differences in response to Sep (during the dark phase of the circadian cycle) were observed in the paradigm used in the present study.

Maternal and perinatal brain aromatase: effects of dietary soy phytoestrogens.

Phytoestrogens are extensively investigated for their potential to prevent many hormone-dependent cancers and age-related diseases, however little is known about their effects in brain. Brain aromatase and plasma phytoestrogen levels were determined in Sprague-Dawley rats fed a phytoestrogen-rich diet during pregnancy/lactation. Ingested phytoestrogens cross the placenta and become concentrated in maternal milk as evident from high infantile plasma concentrations. Dietary phytoestrogens, however, do not alter brain aromatase during pregnancy/lactation or perinatal development.

Sexual dimorphism and aromatase in the rat retina.

The present study: (a) determined the effects of both pre- and early postnatal androgen hormonal manipulation on retinal thickness, (b) examined the presence of the aromatase enzyme by immunocytochemistry in retinal tissue and (c) quantified aromatase activity in the rat retina. The results suggest that retinal thickness is influenced by perinatal hormone manipulation via aromatizable androgens that have implications for the sex differences seen in visual information processing and performance.

Neuroendocrine regulation of sexually dimorphic brain structure and associated sexual behavior in male rats is genetically controlled.

Steroid hormones, particularly 17beta-estradiol (E2), regulate the development and expression of neural structures and sexual behavior. Recently, we demonstrated that E2-regulated responses are controlled by quantitative trait loci. In this study, we quantified 1) volume of the sexually dimorphic nucleus (SDN) of the preoptic area (POA); 2) medial basal hypothalamic (MBH)-POA aromatase and 5alpha-reductase enzyme activities during prenatal development and in adults; 3) serum LH, testosterone, FSH, E2, prolactin (PRL), and corticosterone levels; 4) reproductive organ (i.e., testis and ventral prostate) weights; and 5) male mating behavior in Noble (NB/Cr) and Wistar-Furth (WF/NCr) rat strains to determine the genetic influence on the measured parameters. Maximal phenotypic divergence in male SDN-POA volumes was seen between NB/Cr versus WF/NCr and BDIX/Cr rats (among nine rat strains initially examined), with the average SDN-POA volume of NB/Cr male rats being significantly greater ( approximately 30%) than that of either WF/NCr or BDIX/Cr males. Subsequent experiments investigated WF/NCr versus NB/Cr male rats in further detail. Significantly higher MBH-POA aromatase activity was seen in adult WF/NCr versus NB/Cr males, while MBH-POA 5alpha-reductase rates were not significantly different (within or between sex) for the two rat strains assayed. Serum LH levels were significantly higher (by greater than sixfold) in WF/NCr versus NB/Cr males, whereas testis organ:body weight and ventral prostate:body weight ratios in WF/NCr versus NB/Cr males were significantly smaller (by approximately 6-fold for testis and approximately 1.5-fold for prostate values). Serum FSH levels were significantly higher (by twofold) in WF/NCr versus NB/Cr males. However, serum testosterone levels were not significantly different, whereas E2 levels were approximately twofold higher (but not significantly different) in WF/NCr versus NB/Cr animals. No significant differences were found in basal (i.e., nonstress) serum PRL or corticosterone levels between the WF/NCr and NB/Cr males. In male copulatory tests, NB/Cr males exhibited significantly more aggressive sexual behavior (e.g., in mounting, intromission, and ejaculation parameters) compared with WF/NCr males. Taken together, these findings indicate that WF/NCr males are, in general, low responders, whereas NB/Cr males are high responders to hormonal signals. The obtained data suggest that the correlative, phenotypic variation in SDN-POA volume (i.e., structure) and reproductive hormone patterns and mating behavior (i.e., function) of WF/NCr versus NB/Cr males is regulated by potentially E2-mediated mechanisms that are genetically controlled.

Visual spatial memory is enhanced in female rats (but inhibited in males) by dietary soy phytoestrogens.

BACKGROUND: In learning and memory tasks, requiring visual spatial memory (VSM), males exhibit superior performance to females (a difference attributed to the hormonal influence of estrogen). This study examined the influence of phytoestrogens (estrogen-like plant compounds) on VSM, utilizing radial arm-maze methods to examine varying aspects of memory. Additionally, brain phytoestrogen, calbindin (CALB), and cyclooxygenase-2 (COX-2) levels were determined. RESULTS: Female rats receiving lifelong exposure to a high-phytoestrogen containing diet (Phyto-600) acquired the maze faster than females fed a phytoestrogen-free diet (Phyto-free); in males the opposite diet effect was identified. In a separate experiment, at 80 days-of-age, animals fed the Phyto-600 diet lifelong either remained on the Phyto-600 or were changed to the Phyto-free diet until 120 days-of-age. Following the diet change Phyto-600 females outperformed females switched to the Phyto-free diet, while in males the opposite diet effect was identified.Furthermore, males fed the Phyto-600 diet had significantly higher phytoestrogen concentrations in a number of brain regions (frontal cortex, amygdala & cerebellum); in frontal cortex, expression of CALB (a neuroprotective calcium-binding protein) decreased while COX-2 (an inducible inflammatory factor prevalent in Alzheimer's disease) increased. CONCLUSIONS: Results suggest that dietary phytoestrogens significantly sex-reversed the normal sexually dimorphic expression of VSM. Specifically, in tasks requiring the use of reference, but not working, memory, VSM was enhanced in females fed the Phyto-600 diet, whereas, in males VSM was inhibited by the same diet. These findings suggest that dietary soy derived phytoestrogens can influence learning and memory and alter the expression of proteins involved in neural protection and inflammation in rats.

Manipulation of prenatal hormones and dietary phytoestrogens during adulthood alter the sexually dimorphic expression of visual spatial memory.

BACKGROUND: In learning and memory tasks, requiring visual spatial memory (VSM), males exhibit higher performance levels compared to females (a difference attributed to sex steroid hormonal influences). Based upon the results from our companion investigation, this study examined the influence of prenatal sex steroid hormone manipulations on VSM in adulthood, as assessed in the radial arm maze. Additionally, the influence of dietary soy phytoestrogens (i.e., the presence of high or low estrogen-like compounds present in the animal's diet) on VSM was examined in combination with the prenatal hormonal manipulations. RESULTS: Radial arm maze performance on a phytoestrogen-rich diet: 1) females treated prenatally with testosterone were masculinized and acquired/performed in a manner similar to control or oil-treated males and 2) males treated prenatally with an androgen receptor blocker (flutamide) were feminized and acquired/performed in a fashion typical of control or flutamide-treated females. When a diet change was initiated in adulthood, control phytoestrogen-rich fed females outperformed control females switched to a phytoestrogen-free diet. Whereas, in control males the opposite diet effect was identified. Furthermore, flutamide-treated males fed a phytoestrogen-rich diet outperformed flutamide-treated males switched to a phytoestrogen-free diet. CONCLUSIONS: These results suggest that prenatal hormonal manipulations significantly sex-reverse the normal sexually dimorphic expression of VSM. Specifically, VSM was enhanced in females treated with testosterone and inhibited in males treated with flutamide. Finally, dietary soy phytoestrogens set a bias on learning and memory in these hormonally manipulated animals in a predictable manner and these data confirm and extend the findings in our companion paper.

Pre- or postnatal testosterone and flutamide effects on sexually dimorphic nuclei of the rat hypothalamus.

Utilizing the sexually dimorphic nature of hypothalamic nuclei, a determination of the effects of pre- or postnatal flutamide and testosterone treatments were examined in male and female rats. Statistical analysis compared treatments, sex, and time of injection in terms of the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the anteroventral periventricular nucleus (AVPV) volumes and lengths. The present findings establish that pre- or postnatal hormonal environments are crucial in influencing sexual morphology on the developing brain.

Phytoestrogens decrease brain calcium-binding proteins but do not alter hypothalamic androgen metabolizing enzymes in adult male rats.

Phytoestrogen [plant estrogenic-like molecule(s)] research has grown rapidly in recent years due to their potential health benefits. However, little is known about phytoestrogen's effects on the CNS. Androgen metabolizing enzymes are known to regulate neuroendocrine functions and reproductive behaviors, while calcium-binding proteins are associated with protecting against neurodegenerative diseases. Therefore, we examined aromatase and 5alpha-reductase enzyme activities in the medial basal hypothalamic and preoptic area (mbh-poa) and characterized mbh-poa and amygdala (amy) calbindin and calretinin levels (via Western analysis) from animals fed a phytoestrogen-free (P-free) vs. a phytoestrogen-containing diet [(P-600); that had 600 microg/g of phytoestrogens]. After approximately 5 weeks on the diets, the male rats were killed at 105 days. P-600 plasma phytoestrogen levels were 78-fold higher than the P-free values and the mbh-poa phytoestrogen content was 8-fold higher than the P-free group, demonstrating the passage of phytoestrogens into brain. In general, brain aromatase or 5alpha-reductase activity levels were not significantly altered by the experimental diets. However, independent of brain site (i.e., mbh-poa or amy) the abundance of calbindin from male P-600 rats was significantly lower than P-free animals. Conversely, for calretinin there were no significant alterations in the mbh-poa tissue site, while in the amy a similar pattern of expression was seen to that of the calbindin results. These data suggest that consumption of phytoestrogens via a soy diet for a relatively short interval can significantly: (1) elevate plasma and brain phytoestrogens levels and (2) decrease brain calcium-binding proteins without altering brain androgen metabolizing enzymes.

Dimorphic expression of medial basal hypothalamic-preoptic area calbindin-D(28K) mRNA during perinatal development and adult distribution of calbindin-D(28K) mRNA in Sprague-Dawley rats.

The calcium-binding protein, calbindin (CALB) is: (a) distributed throughout the central nervous system (CNS), (b) abundant in neurons and, (c) thought to act as a buffer by binding intracellular calcium, mediating neurogenesis (cell profileration) and neuronal programmed cell death. Using Northern analysis, CALB mRNA distribution was characterized in 12 different adult brain regions. Additionally, CALB mRNA levels were characterized in the medial basal hypothalamus (MBH) and preoptic area (POA) in perinatal male and female rats, in order to compare this mRNA pattern to the dimorphic MBH-POA CALB protein profile our laboratory previously reported. Three CALB mRNA species were detected (at 1.9, 2.8 and 3.2 kilobase pairs) in all CNS regions. The smallest mRNA transcript (at 1.9 kilobase pairs) was the most abundant of the three CALB mRNAs. To quantify these mRNA signals, CALB mRNA levels were normalized to 18s ribosomal RNA bands. Among the various adult brain sites assayed, the cerebellum expressed the highest CALB mRNA signals. High CALB mRNAs were observed in the MBH-POA, olfactory bulb and hippocampal regions. Moderate CALB mRNA levels were seen in the striatum and frontal cortex while moderate to low CALB mRNA levels were observed in the posterior cortex, entorhinal cortex, midbrain, pons, thalamus and medulla. During perinatal development, MBH-POA CALB mRNA levels were lowest at gestation day (GD) 18, increased four-fold in newborns and remained at moderate levels during early postnatal development. Male CALB mRNA levels were notably greater than female values at GD 18 and in newborns. Whereas, at PND 2, the CALB mRNA levels were approximately equivalent in males and females. These findings suggest that in the adult CNS CALB mRNAs vary among different brain regions. The present male vs. female MBH-POA CALB mRNA levels confirm previously reported dimorphic protein patterns of MBH-POA CALB during perinatal development. Thus, the genesis of sexually dimorphic structures may be influenced by the dimorphic CALB expression in the MBH-POA region.

Relationship between sexual behavior and sexually dimorphic structures in the anterior hypothalamus in control and prenatally stressed male rats.

The present study was designed to examine the effects of prenatal stress on the morphological development of sexually dimorphic structures in the anterior hypothalamus in male rats and to determine if there is a relationship between morphologic development of the brain and copulatory behavior in individual animals. Dams in the stress group were subjected to treatments of heat-light restraint during the third trimester of gestation (day 14 to parturition) three times daily for 45-min periods. At 90 days of age, prenatally stressed and control male offspring were tested during the dark cycle for spontaneous male sexual behavior. Volumes of the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the anteroventral periventricular nucleus (AVPV) were measured. Comparisons were made between copulatory behavior and hypothalamic nuclear volumes. SDN-POA volumes were significantly reduced (feminized; males have a larger SDN-POA than females) in prenatally stressed males that did not copulate, whereas, SDN-POA volumes in prenatally stressed males that copulated were not altered. The few control males that did not copulate (sexually non-active) also had significantly reduced SDN-POA volumes compared to the control males that did copulate (sexually active). The volume of the AVPV was significantly increased (feminized; males have a smaller AVPV than females) in prenatally stressed males that were sexually non-active compared to AVPV volumes in sexually active males. The results obtained in this study provide a strong positive relationship between sexual behavior and the morphology of the two sexually dimorphic structures measured.

Maternal separation: hypothalamic-preoptic area and hippocampal calbindin-D28K and calretinin in male and female infantile rats.

Calcium-binding proteins (CaPs) potentially play important roles in neurogenesis and neuronal survival. Calbindin-D28K (CALB) and calretinin (CALRET) in the medial basal hypothalamic (and preoptic area) (MBH) and hippocampus (HIPPO) from control and maternally separated male and female infantile rats were examined by Western analysis. Significantly greater levels of the CaPs in the MBH vs. the HIPPO may suggest enhanced or decreased neuroprotection, respectively, during the stress hyporesponsive period (SHRP). Male infantile rats separated from their mother's from postnatal day 2-10 displayed significant changes in CALB and CALRET for the MBH (decrease) and HIPP (increase) brain sites suggesting possible modified (negative feedback) mechanism(s) in HPA dysfunction observed during postnatal life.

Brain aromatase in control versus castrated Norway Brown, Sprague-Dawley and Wistar adult rats.

Brain aromatase cytochrome P450 converts androgens to estrogens that play a critical role in the development of sexually dimorphic neural structures, the modulation of neuroendocrine function(s), and the regulation of sexual behavior. We characterized the influence of surgical castration on brain aromatase in Norway Brown and Wistar adult rats and compared their responses to Sprague-Dawley rats that were surgically or biochemically castrated (with flutamide, a known androgen receptor blocker). Aromata enzyme activity was measured by the tritiated water release assay in the medial basal hypothalmus/preoptic area (MBH/POA) and amygdala brain regions. The present results demonstrate that independent of the rat strain examined, MBH/POA aromatase is regulated by androgens (in Sprague-Dawley, Norway Brown and Wistar males). However, intact Wistar animals displayed significantly higher MBH/POA aromatase levels compared to Sprague-Dawley control values. Conversely, in the amygdala region, there was an apparent lack of androgen hormone action upon aromatase enzyme activity in some of the rat strains tested. The importance of brain aromatase regulating estrogen biosynthesis and influencing brain development and function is covered.

Brain aromatase and 5alpha-reductase, regulatory behaviors and testosterone levels in adult rats on phytoestrogen diets.

The purpose of this study was to examine the short-term effects of phytoestrogens in the diet on regulatory behaviors (food/water intake and locomotor activity), prostate weight, testosterone levels, and brain androgen metabolizing enzyme activity levels in adult male rats. Sprague-Dawley rats were fed phytoestrogen-containing versus phytoestrogen-free diets for 29 days. Standard methods were used to measure open field behavior, reproductive, hormonal parameters, and enzymatic activity levels. The phytoestrogen diet contained approximately 200 microg/g of isoflavones whereas in the phytoestrogen-free diet, no phytoestrogens were detected by HPLC analysis. There were no significant differences in any of the regulatory behaviors (food/water intake or locomotor activity), prostate weight, or testosterone levels between the treatment groups. Furthermore, there was no significant influence of phytoestrogens on brain aromatase activity levels, in either the medial basal hypothalamic-preoptic area (MBH-POA) or amygdala brain tissue sites examined. However, significant alterations in MBH-POA and amygdala 5alpha-reductase activities were detected in animals receiving the phytoestrogen-containing versus the phytoestrogen-free diets.