Apparent effects of neurotransmitters on sexual differentiation of the brain without mediation of sex hormones.

Male sexual behaviour was found to be permanently decreased in neonatally reserpinized or paragylinized male rats. On the other hand, hypoplasia of sex organs was only observed in reserpinized, but not in pargylinized newborn males. Furthermore, male sexual behavior was found to be permanently increased in neonatally pyridostigminized males which showed even a slight hypoplasia of seminal vesicles in neonatal life. These findings suggest that changes of neurotransmitter concentrations and/or turnover rates apparently induced by psychotrophic drugs can affect sex-specific brain differentiation by direct action without mediation of sex hormones. Hence, neurotransmitters may be regarded as organizers of the brain.     

Sex hormones and neurotransmitters as mediators for sexual differentiation of the brain

Sexual differentiation of the brain is regarded as a model for environment-dependent brain development mediated by systemic hormones and neurotransmitters. Abnormal concentrations of systemic hormones and/or neurotransmitters, if occurring during a critical period of brain development, can lead to permanent developmental disabilities of fundamental processes of life. Such developmental disabilities appear to be avoidable, at least in part, by improving the external, i.e. psychosocial and natural environment, or by correcting abnormalities in the internal, i.e. metabolic and hormonal environment and, particularly, by correcting abnormal neurotransmitter concentrations (and/or turnover rates) during brain development.     

Sex hormone receptors in the hypothalamus and their role in the sexual differentiation of the brain of male rats

The content of receptors to estradiol and testosterone was determined in cytoplasmic and nuclear fractions of hypothalamus and brain cortex of male rats in the early postnatal period. Receptors to both estradiol and testosterone were revealed in cytosol and nuclear fractions, with the decrease in their concentration observed from days 1 to 5. The data obtained demonstrate that receptors to sexual hormones take part in the brain differentiation and regulation of hypophysis gonadotropic function by male or female type.     

糖尿病大鼠性腺及外周血中性激素的改变

目的:研究糖尿病大鼠性腺及外周血中性激素的变化。方法:用放射免疫法检测糖尿病(DM)大鼠,正常(NDM)大鼠和STZ大鼠血清性激素含量,同时称取性腺重量,镜检睾丸、前列腺及附睾的组织形态学改变。结果:DM组睾酮水平显著低于NDM组、STZ组(P<0.01);NDM组与STZ组之间,睾酮水平无显著性差异;DM组促黄体生成素(LH)水平显著高于NDM组、STZ组(P<0.01);NDM组与STZ组之间。LH水平无显著性差异;促卵泡刺激素(FSH)水平在各组之间无显著性差异;HE结果显示,DM组性腺显微结构较NDM组及STZ组明显改变。结论:提示DM严重影响大鼠性腺功能及睾酮的合成分泌,并显著降低大鼠血清睾酮含量。     

Steroid hormones and their receptors in the brain

Steroid hormones regulate several important functions of the brain by altering the expression of particular genes through their receptors. First in this paper the localization of glucocorticoid receptor immunoreactivity and mRNA in the brain was examined. Second biphasic effects of glucocorticoid on the hippocampus was described and particular emphasis was given on the apoptosis. Third the significance of estrogen receptor in the sexually dimorphic areas was discussed. These results suggest that steroids modulate the gene expression along with the alteration of cell structures in a different manner in a tissue-specific pattern.     

Changes in secretion of sex steroid hormones during stress in rats with various brain excitability

A stress procedure decreased the plasma progesterone faster in highly excitable rats than in the less excitable those. The decrease in gonadal and adrenal progesterone was still obvious in 24 hours in both groups of rats but more obvious in the former group in respect to the progesterone level. The data obtained may help to understand individual ability to respond to a stress in a different way depending on functional condition of the hypothalamo-pituitary-adrenal axis.     

Hormonally mediated epigenetic changes to steroid receptors in the developing brain: Implications for sexual differentiation

The establishment of sex-specific neural morphology, which underlies sex-specific behaviors, occurs during a perinatal sensitive window in which brief exposure to gonadal steroid hormones produces permanent masculinization of the brain. In the rodent, estradiol derived from testicular androgens is a principal organizational hormone. The mechanism by which transient estradiol exposure induces permanent differences in neuronal anatomy has been widely investigated, but remains elusive. Epigenetic changes, such as DNA methylation, allow environmental influences to alter long-term gene expression patterns and therefore may be a potential mediator of estradiol-induced organization of the neonatal brain. Here we review data that demonstrate sex and estradiol-induced differences in DNA methylation on the estrogen receptor α (ERα), estrogen receptor β (ERβ), and progesterone receptor (PR) promoters in sexually dimorphic brain regions across development. Contrary to the overarching view of DNA methylation as a permanent modification directly tied to gene expression, these data demonstrate that methylation patterns on steroid hormone receptors change across the life span and do not necessarily predict expression. Although further exploration into the mechanism and significance of estradiol-induced alterations in DNA methylation patterns in the neonatal brain is necessary, these results provide preliminary evidence that epigenetic alterations can occur in response to early hormone exposure and may mediate estradiol-induced organization of sex differences in the neonatal brain.     

Evidence that sex chromosome genes affect sexual differentiation of female sexual behavior

Female receptivity including the immobile hormone-dependent lordosis posture is essential for successful reproduction in rodents. It is well documented that lordosis is organized during the perinatal period when the actions of androgens decrease the males' ability to display this behavior in adulthood. Conversely the absence of androgens, and the presence of low levels of prepubertal estrogens, preserve circuitry that regulates this behavior in females. The current study set out to determine whether sex chromosomal genes are involved in the differentiation of this behavior. An agonadal mouse model was used to test this hypothesis. The SF-1 gene (Nr5a1) is required for development of gonads and adrenal glands, and knockout mice are consequently not exposed to endogenous gonadal steroids. Thus contributions of sex chromosome genes can be disassociated from the actions of estrogens. Use of this model reveals a direct genetic contribution from sex chromosomes in the display of lordosis and other female-typical sexual behavior patterns. It is likely that the concentrations of gonadal steroids present during normal male development modify the actions of sex chromosome genes on the potential to display female sexual behavior.     

Hypothalamic excitatory amino acid system during sexual maturation in female rats

The present results indicate that during sexual maturation the APOA-MBH from rats of 30 days of age released significantly higher quantities of GnRH than the tissue from 16-day-old rats (P < 0.01). The addition of NMDA, an agonist of the excitatory amino acids system (EAAs), to the medium after 30 min of incubation significantly increased (P < 0.01) the GnRH release in normal rats of both ages and this increase was significantly (P < 0.01) higher in 30-day-old rats (to 661%) than in rats of 16 days of age (to 273%). The administration of estrogen-progesterone (EP) to rats of 16 days of age did not modify the GnRH release response to NMDA. On the contrary, at 30 days of age EP administration significantly potentiated the GnRH release response to NMDA since while in the control group NMDA increased the GnRH release to 630%, in the EP-pretreated group this was to around 4700% (P < 0.01). EP pretreatment of prepubertal rats decreases the hypothalamic release of aspartate and glutamate, the excitatory amino acids involved in NMDA neurotransmission and glycine but increases EAAs release in peripubertal rats. On the basis of these results it is proposed that the increase in EAAs release by the hypothalamus is directly connected with the onset of puberty and that the maturation of the positive feedback effect of ovarian hormones on gonadotropin secretion is related to the maturation of the capacity of EP to increase hypothalamic EAAs. Before this maturational event EP inhibits EAAs release as well as gonadotropin release (prepubertal rats). NMDA receptor stimulation leads to a positive mechanism which increases the release of Asp and Glu from APOA-MBH both in prepubertal and peripubertal rats, but EP potentiates this mechanism only in peripubertal rats. This could be an additional neuroendocrine mechanism involved in the increase of gonadotropin during sexual maturation which induces the onset of puberty and the preovulatory discharge of these pituitary hormones.     

Progesterone receptors and the sexual differentiation of the medial preoptic nucleus

The central component of the medial preoptic nucleus (MPNc) of the rat has served as an excellent model of sexual differentiation. The MPNc is larger in adult males than in females, and its development is regulated by perinatal gonadal hormones. Although testosterone (T) and its metabolite estradiol (E) sexually differentiate this region, the exact mechanism by which they act during development is not known. There is a dramatic sex difference in the expression of progesterone receptors (PR) in the MPN during development; perinatal males express higher levels of PR than females. Additionally, PR expression during this time is dependent on exposure to T. Thus, PR induction may be one mechanism by which T sexually differentiates the MPN. The present study investigated the potential role of PR in the sexual differentiation of the MPNc. Anatomical examination of PR distribution within the MPN of neonatal males revealed the presence of PR immunoreactive cells within the MPNc, suggesting a direct route of action for PR in the development of the MPNc. Additionally, we measured the effects of neonatal RU486 treatment, a progesterone and glucocorticoid receptor antagonist, on subsequent MPNc volume in neonatally T-treated females and neonatally castrated males, given T. RU486 treatment reduced the MPNc volume of T-treated females while it increased the volume in T-treated, neonatally castrated males. These results, taken together with the expression of PR in the MPNc, suggest that PR may influence the sexual differentiation of the MPNc volume.     

Development of the renal sexual segment in immature snakes: effect of sex steroid hormones

The renal sexual segment (RSS) of immature Northern and Diamondback Water Snakes and Red-Sided Garter Snakes exhibited varying responses to testosterone or 17beta-estradiol. In both male and female water snakes, kidney mass was not a reliable indicator of hormone treatment, whereas tubule diameter, epithelial height and number of sexual granules responded to hormone treatment. In male water snakes, either hormone initiated granule development by day 16; by day 23, only testosterone increased granule density. Female water snakes receiving either hormone exhibited a small number of granules by day 16; by day 23, granules increased only in Diamondback Water Snakes receiving testosterone. Hormones did not initiate RSS hypertrophy in female Red-Sided Garter Snakes. Tubule diameter and epithelial height of testosterone-treated males exhibited significant hypertrophy, while 17beta-estradiol initiated significant increases in tubule diameter. Garter snakes initiated sexual granule development in response to hormone treatment with males exhibiting a greater response than females and testosterone stimulating a greater response than 17beta-estradiol. Sex steroids appear to mimic sexual maturity in immature snakes initiating RSS development. Whereas the RSS of adult males respond to testosterone, our data suggest specific changes in the RSS of females during maturation effectively negates the effect of 17beta-estradiol evident in immature female RSS.