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C E Roselli

Publications and source records attributed to C E Roselli.

At least 19 recordsLinked to original sources
PubMed2007

Neuronal activity of aromatase enzyme in non-copulating male rats.

There are apparently normal male rats that fail to initiate copulation; these animals are called non-copulating (NC) males. Several research groups have demonstrated that conversion of testosterone to oestradiol (aromatisation) in specific brain areas known to be involved in the control of masculine sexual behaviour is fundamental in the control of masculine sexual behaviour. The aim of the present study was to test the hypothesis that the concentration of aromatase activity (AA) in the brain is lower in NC males than in copulating males (C). We quantified AA in several brain nuclei and also evaluated whether NC rats have altered concentrations of testosterone in their plasma. We found that AA was reduced in the medial preoptic nuclei (MPN) of NC male rats vs C males. In addition, NC and C male rats had similar plasma levels of testosterone. These data suggest that reduced levels of AA in the MPN could be a crucial factor associated with lack of male coital behaviour in rats.

Animals↗
PubMed2006

The effect of aromatase inhibition on the sexual differentiation of the sheep brain.

This study tested the hypothesis that aromatization of testosterone to estradiol is necessary for sexual differentiation of the sheep brain. Pregnant ewes (n = 10) were treated with the aromatase inhibitor 1,4,6- androstatriene-3,17-dione (ATD) during the period of gestation when the sheep brain is maximally sensitive to the behavior-modifying effects of exogenous testosterone (embryonic d 50-80; 147 d is term). Control (n = 10) ewes received vehicle injections. Fifteen control lambs (7 males and 8 females) and 17 ATD-exposed lambs (7 males and 10 females) were evaluated for sexually dimorphic behavioral and neuroendocrine traits as adults. Prenatal ATD exposure had no significant effect on serum concentrations of androgen at birth, growth rates, expression of juvenile play behaviors, or the onset of puberty in male and female lambs. Rams exposed to ATD prenatally exhibited a modest, but significant, decrease in mounting behavior at 18 mo of age. However, prenatal ATD exposure did not interfere with defeminization of adult sexual partner preferences, receptive behavior, or the LH surge mechanism. In summary, our results indicate that aromatization is necessary for complete behavioral masculinization in sheep. However, before we can conclude that aromatization does not play a role in defeminization of the sheep brain, it will be necessary to evaluate whether intrauterine exposure of male fetuses to higher doses of ATD for a more extended period of time can disrupt normal neuroendocrine and behavioral development.

Androstatrienes↗
PubMed2004

Distribution of aromatase activity in brain and peripheral tissues of male sheep: effect of nutrition.

Conversion of testosterone to oestradiol plays a major role in the feedback inhibition of gonadotrophin secretion in male sheep but little is known of the distribution or control of aromatase activity among central and peripheral tissues. Changes in activity at those sites may mediate alterations in the effectiveness of negative feedback following, for example, a change in nutrition. Using a tritiated-water assay, we quantified aromatase in several tissues in mature male sheep, assessed their contribution to oestradiol production, and tested whether activity at each site was affected by a nutritional treatment that stimulates gonadotrophin secretion. Among the brain tissues, the preoptic area had the highest concentration of activity, followed by the hypothalamus, amygdala and cortex. Among the peripheral tissues, liver and testis had the highest activity and, due to their mass, they are the major sources of circulating oestradiol. Pituitary, muscle, kidney and adipose tissues had very low aromatase levels. The nutritional stimulus increased activity in testis but not in liver or brain. We conclude that changes in aromatase activity do not mediate the effects of nutrition on steroid feedback, but aromatisation in testis, liver and brain is important in the endocrine regulation of reproduction in the mature ram.

Animal Nutritional Physiological Phenomena↗
PubMed2003

Role of aromatization in anticipatory and consummatory aspects of sexual behavior in male rats.

The present study was designed to test the hypothesis that aromatization is involved in the maintenance by testosterone of the appetitive component of male sexual behavior. We measured appetitive sexual behavior by administering behavioral tests in bilevel chambers and quantifying anticipatory level changes during a 5-min period prior to introduction of a stimulus female. In addition, we recorded standard measures of consummatory male sexual behavior after the female was introduced. Following 3 weekly tests, level-changing behavior reached a plateau and remained stable for up to 10 weeks. After 10 bilevel tests, rats were given subcutaneous testosterone capsules to clamp circulating androgen at physiological levels. Rats were tested and divided into two groups that were matched for measures of sexual behavior. One group was then treated with the nonsteroidal aromatase inhibitor, Fadrozole (2.5 mg/kg/day), given subcutaneously in beta-cyclodextrin and the other group was treated with vehicle. Within 1 week of Fadrozole treatment, the number of anticipatory levels changes was significantly reduced, but not the latency to begin searching. Fadrozole treatment also significantly reduced all measures of copulatory behavior over the period of treatment and increased latencies to first mount, intromission, and ejaculation. After 8 weeks, both treatment groups were given an additional Silastic capsule filled with estradiol and tested for 4 additional weeks. Estrogen treatment partially restored level-changing behavior, mounts, and intromissions but had little effect on ejaculations. These results support the view that aromatization is important for maintaining both the appetitive and the consummatory aspects of sexual behavior in male rats.

Animals↗
PubMed2001

Anatomic relationships between aromatase and androgen receptor mRNA expression in the hypothalamus and amygdala of adult male cynomolgus monkeys.

This study mapped the regional locations of cells expressing cytochrome P450 aromatase (P450AROM) and androgen receptor (AR) mRNAs in the adult male macaque hypothalamus and amygdala by in situ hybridization histochemistry using monkey-specific cRNA probes. High densities of P450AROM and AR mRNA-containing neurons were observed in discrete hypothalamic areas involved in the regulation of gonadotropin secretion and reproductive behavior. P450AROM mRNA-containing neurons were most abundant in the medial preoptic nucleus, bed nucleus of the stria terminalis, and anterior hypothalamic area, whereas AR mRNA-containing neurons were most numerous in the ventromedial nucleus, arcuate nucleus, and tuberomamillary nucleus. Moderate to heavily labeled P450AROM mRNA-containing cells were present in the cortical and medial amygdaloid nuclei, which are known to have strong reciprocal inputs with the hypothalamus. Heavily labeled P450AROM mRNA-containing cells were found in the accessory basal amygdala nucleus, which projects to the cingulate cortex and hippocampus, areas that are important in the expression of emotional behaviors and memory processing. In contrast to P450AROM, the highest density of AR mRNA labeling in the temporal lobe was associated with the cortical amygdaloid nucleus and the pyramidal cells of the hippocampus. All areas that contained P450AROM mRNA-expressing cells also contained AR mRNA-expressing cells, but there were areas in which AR mRNA was expressed but not P450AROM mRNA. The apparent relative differences in the expression of P450AROM and AR mRNA-containing neurons within the monkey brain suggests that T acts through different signaling pathways in specific brain areas or within different cells from the same region.

Amygdala↗
PubMed2001

Cytochrome P450 aromatase (CYP19) in the non-human primate brain: distribution, regulation, and functional significance.

In adult male primates, estrogens play a role in both gonadotropin feedback and sexual behavior. Inhibition of aromatization in intact male monkeys acutely elevates serum levels of luteinizing hormone, an effect mediated, at least partially, within the brain. High levels of aromatase (CYP19) are present in the monkey brain and regulated by androgens in regions thought to be involved in the central regulation of reproduction. Androgens regulate aromatase pretranslationally and androgen receptor activation is correlated with the induction of aromatase activity. Aromatase and androgen receptor mRNAs display both unique and overlapping distributions within the hypothalamus and limbic system suggesting that androgens and androgen-derived estrogens regulate complimentary and interacting genes within many neural networks. Long-term castrated monkeys, like men, exhibit an estrogen-dependent neural deficit that could be an underlying cause of the insensitivity to testosterone that develops in states of chronic androgen deficiency. Future studies of in situ estrogen formation in brain in the primate model are important for understanding the importance of aromatase not only for reproduction, but also for neural functions such as memory and cognition that appear to be modulated by estrogens.

Androgens↗
PubMed2001

Cytochrome P450 aromatase in testis and epididymis of male rhesus monkeys.

To understand the role of estrogen in testicular and epididymal function of rhesus monkeys, we measured steroids in the spermatic and peripheral venus circulation and aromatase activity and its mRNA in testis and epididymis. Testosterone, estradiol-17beta, and estrone, but not androstenedione, were elevated in the spermatic vein serum compared to the peripheral circulation. Aromatase activity in testis and in caput epididymis (259+/-16 [SEM] vs 274+/-47 fmol of 3H2O/mg of protein/h [n = 10], respectively) was significantly higher (p < 0.01) than in corpus and cauda (124+/-28 and 113+/-33 fmol of 3H2O/mg of protein/h [n = 10], respectively). In the ribonuclease protection assay, two P450arom mRNA transcripts were identified in testis and epididymis. One corresponded with the aromatase full-length transcript and the other was a truncated isoform. The latter was significantly more abundant than the former (p < 0.01). Our results demonstrate that the monkey testis and, to a lesser extent, the epididymis can aromatize androgens. However, in the epididymis, like in some areas of the brain, there was a discrepancy between the aromatase activity and the mRNA. The fact that P450arom mRNA and aromatase activity do not correlate in the epididymis may indicate that aromatase activity is not strictly regulated at the level of RNA expression and that other mechanisms for this regulation should be considered.

Animals↗
PubMed2000

Estrogen receptors and aromatase activity in the hypothalamus of the female frog, Rana esculenta. Fluctuations throughout the reproductive cycle.

It is well known that certain actions of androgen are mediated through in situ aromatization to estrogen in neural target tissues. This study was undertaken to investigate androgen utilization in the hypothalamus of the female frog, Rana esculenta, through a quantification of estrogen receptors and aromatase activity during the reproductive cycle. 3H-estradiol-binding molecules were present in both the cytosol and the nuclear extract of the hypothalamus. These molecules bound specifically 3H-estradiol with high affinity (Kd 10(-10) M) and low capacity (cytosol: 1.2+/-0.4 fmol/mg protein; nuclear extract: 7.9+/-0.6 fmol/mg protein). Aromatase activity was detected in the microsomal fraction of the hypothalamus using a sensitive in vitro radiometric assay. Both aromatase activity and nuclear estrogen receptor binding fluctuated in synchrony throughout the reproductive cycle. Western blot analysis of aromatase protein revealed one immunoreactive band with a molecular weight of approximately 56 kDa. In contrast to aromatase enzyme activity, the relative levels of aromatase protein changed little during the reproductive cycle suggesting that post-translational mechanisms may be involved in regulating estrogen synthesis in the frog brain. A possible role for estrogens in the modulation of the reproductive behavior in this species is suggested.

Animals↗
PubMed2000

Distribution of aromatase mRNA in the ram hypothalamus: an in situ hybridization study.

The regional distribution of neurones expressing aromatase mRNA in the ram hypothalamus was examined by in situ hybridization using 33P-labelled cRNA probes. The highest amounts of hybridization signal were observed in the central part of the medial preoptic nucleus and posterior medial part of the bed nucleus of the stria terminalis. Moderate amounts of hybridization signal were observed in the anteroventral periventricular preoptic nucleus, medial preoptic nucleus and a broad band extending between the medial preoptic nucleus and bed nucleus of the stria terminalis. Low levels of hybridization signal were observed in the organum vasculosum of the lamina terminalis, anterior part of the medial preoptic nucleus, and central part of the ventromedial nucleus of the hypothalamus. The presence of aromatase mRNA within neurones of the steroid-sensitive hypothalamic circuit supports a role for aromatization in the mechanism of testosterone action on reproductive function in male sheep. The distribution of aromatase mRNA in the ovine hypothalamus was similar to that described for other vertebrate species, suggesting a high degree of functional conservation across species.

Animals↗
PubMed2000

Region-specific regulation of cytochrome P450 aromatase messenger ribonucleic acid by androgen in brains of male rhesus monkeys.

We demonstrated previously that testosterone regulates aromatase activity in the anterior/dorsolateral hypothalamus of male rhesus macaques. To determine the level of the androgen effect, we developed a ribonuclease protection assay to study the effects of testosterone or dihydrotestosterone (DHT) on aromatase (P450(AROM)) mRNA in selected brain areas. Adult male rhesus monkeys were treated with testosterone or DHT. Steroids in serum were quantified by RIA. Fourteen brain regions were analyzed for P450(AROM) mRNA. Significant elevations of its message over controls (P<0.05) were found in the medial preoptic area/anterior hypothalamus of both androgen treatment groups and the medial basal hypothalamus of the testosterone-treated males. Other brain areas were not affected by androgen treatment. We conclude that testosterone and DHT regulate P450(AROM) mRNA in brain regions that mediate reproductive behaviors and gonadotropin release. The P450(AROM) mRNA of other brain areas is not androgen dependent. Brain-derived estrogens may also be important for maintaining neural circuitry in brain areas not related to reproduction. The control of P450(AROM) mRNA in these areas may differ from what we report here, but it is equally important to understand the function of in situ estrogen formation in these areas.

Androgens↗
PubMed2000

Cellular observations and hormonal correlates of feedback control of luteinizing hormone secretion by testosterone in long-term castrated male rhesus monkeys.

Testosterone at physiological levels cannot exert negative feedback action on LH secretion in long-term castrated male monkeys. The cellular basis of this refractoriness is unknown. To study it, we compared two groups of male rhesus macaques: one group (group 1, n = 4) was castrated and immediately treated with testosterone for 30 days; the second group (group 2, n = 4) was castrated and treated with testosterone for 9 days beginning 21 days after castration. Feedback control of LH by testosterone in group 1 was normal, whereas insensitivity to its action was found in group 2. Using the endpoints of concentrations of aromatase activity (P450(AROM) messenger RNA [mRNA]) and androgen receptor mRNA in the medial preoptic anterior hypothalamus and in the medial basal hypothalamus, we found that aromatase activity in both of these tissues was significantly lower, P: < 0.01, in group 2 compared with group 1 males. P450(AROM) mRNA and androgen receptor mRNA did not differ, however. Our data suggest that the cellular basis of testosterone insensitivity after long-term castration may reside in the reduced capacity of specific brain areas to aromatize testosterone. Because P450(AROM) mRNA did not change in group 2 males, we hypothesize that an estrogen-dependent neural deficit, not involving the regulation of the P450(AROM) mRNA, occurs in long-term castrated monkeys.

Androstenedione↗
PubMed1999

Androgen receptor messenger ribonucleic acid in brains and pituitaries of male rhesus monkeys: studies on distribution, hormonal control, and relationship to luteinizing hormone secretion.

Because the distribution and hormonal regulation of the androgen receptor (AR) mRNA in brains and pituitaries of adult rhesus monkeys have not been studied, we cloned and sequenced a 329-base pair segment of the 5' coding region of the rhesus AR cDNA. Monkey AR cDNA was 99% identical with the human sequence and 96% homologous with the rat sequence. Using a ribonuclease protection assay, we studied the distribution and regulation of AR mRNA in brains and anterior pituitary glands of three groups of male rhesus monkeys: intact (n = 3), castrated (Cx, n = 4), and Cx treated with testosterone (n = 6). Serum testosterone levels of Cx males treated with testosterone differed significantly (p < 0.05) in the morning but not in the evening hours from those in intact controls. Serum LH concentrations were significantly suppressed (p < 0.05) in both morning and evening serum samples of testosterone-treated males compared to intact controls. We found the highest concentrations of AR mRNA in the medial basal hypothalamus, the bed nucleus of the stria terminalis, the medial preoptic area-anterior hypothalamus, and the lateral dorsomedial hypothalamus. Intermediate amounts were found in the septum and amygdala. Low amounts were found in the hippocampus, cingulate cortex, parietal cortex, and cerebellum. The anterior pituitary gland also contained a large amount of AR mRNA. Surprisingly, neither Cx for 3 wk nor Cx plus testosterone replacement for 3 wk significantly affected AR mRNA in any brain area or in the pituitary gland. The present study demonstrates that the effectiveness of testosterone as a regulator of LH secretion in male monkeys is not related to changes of AR mRNA in the brain or pituitary gland. It appears that AR mRNA in the monkey brain and pituitary gland is not regulated at the transcriptional level by androgen.

Animals↗
PubMed1999

17beta-estradiol rapidly facilitates chemoinvestigation and mounting in castrated male rats.

Testosterone and estradiol act synergistically to stimulate male sexual behavior. Previous studies demonstrated that testosterone's actions are mediated genomically. Attempts to show that estradiol acts in a similar fashion have been inconclusive. However, estrogens have been shown to exert short-latency effects by acting directly on neuronal membranes. The present experiment examined whether testosterone or estradiol rapidly facilitates copulatory behaviors in castrated sexually experienced rats. Within 35 min of administration, estradiol stimulated chemoinvestigation and frequency of mounting and reduced mount latency in a dose-dependent manner. In contrast, acute administration of testosterone did not alter sexual activity. These data demonstrate for the first time that estradiol exerts short-latency effects on copulatory behavior, providing indirect evidence that this action is mediated through a nontranscriptional mechanism.

Animals↗
PubMed1999

Sex differences in male-typical copulatory behaviors in response to androgen and estrogen treatment in rats.

The present experiment was performed to test the hypothesis that gender differences in the capacity for brain estrogen synthesis could constitute a sexually dimorphic mechanism that limits the activational effects of testosterone (T) in females, and enhances them in males. We determined the effects of treatments with equivalent levels of either T or estradiol (E2) on olfactory behavior and mounting in age-matched heterosexually naive gonadectomized male and female rats that were genitally ansthetized with lidocaine paste in order to minimize the contribution of sexually dimorphic somatosensory inputs to the expression of copulatory behavior. We found that T stimulated mounting to a greater extent in males than in females, but had equivalent effects on mount latency and genital investigation in the two sexes. On the other hand, E2 stimulated equivalent levels of mounting in males and females and reduced mount latency to a similar extent in males and females. However, E2 had a pronounced effect on the levels of genital investigation in males but not in females. Serum steroid levels and the levels of nuclear steroid receptor occupation in the brain were not different between males and females, suggesting that the behavioral differences between males and females cannot be attributed to differences in peripheral steroid metabolism or brain uptake. The results obtained corroborate previous studies suggesting that female rats normally undergo considerable male-typical behavioral masculinization during fetal development. However, such male-typical features of normal development in female rats do not extend to the regulation of preoptic aromatase activity or to the capacity of females to display olfactory behaviors in response to adult E2 exposure, functions which are sexually dimorphic even in the rat. The present results support the view that gender differences in the capacity for brain estrogen synthesis contribute to the sexually dimorphic display of T-stimulated male-typical sexual motivation and copulatory behavior in rats.

Animals↗
PubMed1999

Sexual behaviour of rams: male orientation and its endocrine correlates.

The components of heterosexual behaviour in rams are reviewed as a basis for understanding partner preference behaviour. A small percentage of rams will not mate with oestrous females and if given a choice will display courtship behaviour towards another ram in preference to a female. Some of the endocrine profiles of these male-oriented rams differ from those of heterosexual controls. These differences include reduced serum concentrations of testosterone, oestradiol and oestrone, reduced capacity to produce testosterone in vitro, and reduced capacity to aromatize androgens in the preoptic-anterior hypothalamus of the brain. Our observation that aromatase activity is significantly lower in the preoptic-anterior hypothalamic area of male-oriented rams than in female-oriented rams may indicate an important neurochemical link to sexual behaviour that should be investigated. The defect in steroid hormone production by the adult testes of the male-oriented ram may represent a defect that can be traced to the fetal testes. If this contention is correct, partner preference behaviour of rams may also be traceable to fetal development and represent a phenomenon of sexual differentiation.

Animals↗
PubMed1998

Distribution and regulation of aromatase activity in the ram hypothalamus and amygdala.

Conversion of androgen to estrogen within the brain by cytochrome P450 aromatase is a component of the system controlling the display of normal male reproductive behavior and negative feedback inhibition of LH secretion in rams. In the present study, we used the highly sensitive 3H2O assay to measure aromatase activity in microdissected regions of the basal diencephalon and amygdala of intact and castrated rams. We found that aromatase activity was heterogeneously distributed. The highest activity was found in the medial amygdala, cortical amygdala, and bed nucleus of the stria terminalis. Intermediate levels of aromatase activity were found within the medial preoptic area/anterior hypothalamus, periventricular preoptic area, lateral preoptic area/anterior hypothalamus, ventromedial hypothalamus, and lateral hypothalamus. The lowest activity was present in the septum, infundibulum/median eminence, and dorsal medial hypothalamus. After castration, aromatase was significantly reduced in the medial preoptic area/anterior hypothalamus, periventricular preoptic area, lateral preoptic area/anterior hypothalamus, and infundibular nucleus/median eminence. In contrast, levels in castrate rams were unchanged in several other regions, most notably the bed nucleus of the stria terminalis and medial and cortical amygdala. These results provide a quantitative profile of aromatase activity in discrete regions of the ram hypothalamus and limbic system. They also demonstrate that aromatase activity is reduced in some, but not all brain regions after castration which suggests that different regulatory mechanisms control aromatase within different neuronal populations of the ram.

Amygdala↗
PubMed1998

The effect of anabolic-androgenic steroids on aromatase activity and androgen receptor binding in the rat preoptic area.

The level of aromatase in the preoptic area of rats is transcriptionally regulated through a specific androgen-receptor mediated mechanism and can be used as a measure of central androgenic effect. Therefore, several commonly abused anabolic-androgenic steroids (AAS) were tested for their ability to induce aromatase activity in the preoptic area of castrated rats. In addition, we determined the relative binding affinities of these compounds for the androgen receptor, as well as their ability to bind androgen receptor in vivo following subcutaneous injections. All of the AAS compounds tested significantly stimulated POA aromatase activity above castrate levels. The compounds that produced the greatest stimulation of aromatase activity were those that bound most avidly to the androgen receptor in vitro (i.e., testosterone, dihydrotestosterone and nandrolone). In contrast, the 17alpha-alkylated compounds that were tested (stanozolol, danazol, methandrostenolone) modestly stimulated aromatase and were weak competitors for the androgen receptor. The subcutaneous injection of AAS compounds increased the concentrations of occupied nuclear androgen receptors in the brain, but the magnitude of effect was not related to their potency for inducing aromatase or their relative binding affinity for the androgen receptor suggesting that androgen receptor occupancy in POA is not correlated with the action of androgen on aromatase. The present results help explain the behavioral effects of AAS compounds in rats.

Anabolic Agents↗