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PubMed2004

Pubertal development of sex differences in circadian function: an animal model.

UNLABELLED: The development of adult circadian function, particularly sexual dimorphism of function, has been well studied only in rapidly developed rodents. In such species development is complete by weaning. Data from adolescent humans suggest that significant development occurs during the pubertal period. We hypothesized that a more slowly developing rodent might better mimic the changes in circadian function around puberty in humans and allow us to determine the underlying neural changes. Entrained and free-running circadian rhythms were analyzed and correlated with pubertal development in male and female Octodon degus (degu) that remained gonadally intact or were gonadectomized at weaning. Brains were collected during development to measure androgen and estrogen receptors in the suprachiasmatic nuclei (SCN) Adult circadian period does not develop until 10-12 months of age in degus, long after the onset of gonadal maturation (3-5 months). The timing of circadian period maturation correlates with the appearance of steroid receptors in the SCN. Changes in free-running rhythms only occurred in gonadally intact degus. Adult phase angles of activity onset develop between 2 and 3 months of age (comparing results of two experiments), soon after the onset of pubertal changes. CONCLUSION: The development of sexually dimorphic adult circadian period occurs after gonadal puberty is complete and requires the presence of gonadal steroids. The delay in development until after gonadal puberty is likely due to the delayed appearance of steroid receptors in the SCN. Phase is not sexually dimorphic and changes in the absence of steroid hormones.

Age Factors↗
PubMed2004

Postnatal apoptosis, development, and sex difference in the lateral septum of rats.

To determine whether apoptosis is involved in the formation of the structure and morphological sex difference of the lateral septum (LS), the postnatal developmental changes in the number of apoptotic cells were examined in the LS on postnatal day 1 (PD1 = birth day), 4, 6, 8, 11, 16, and 31 in male and female rats. Apoptotic cells were immunohistochemically detected by antibody against single-stranded DNA (ssDNA) or active caspase-3. The volume of the LS was also measured and was found to increase with age. The number of apoptotic cells detected by anti-ssDNA in the LS increased from PD1 to PD8 but decreased after PD11. Also, the LS was divided into dorsal, intermediate, and ventral parts (LSd, LSi, and LSv), and the volume and number of ssDNA-immunoreactive cells in each part were measured on PD6, 8, 11, 16, and 31. In both sexes, a large number of ssDNA-immunoreactive cells was found in the LSd and LSi on PD8 (but not on PD6) and in the LSv on PD6 and PD8. On PD6, the number of active caspase-3-immunoreactive cells was significantly greater in the LSv than in the LSd or LSi, in both sexes. Only the LSi of males had a high number of ssDNA-immunoreacitve cells on PD16; the number was significantly greater than that of females of the same age. However, there was no significant sex difference in the number of active caspase-3-immunoreacitve cells in the LSi on PD16. On PD31, the volume of the LSi was significantly greater in females than in males. There was no sex difference in volume or number of apoptotic cells in the LSd or LSv. These findings indicate that loss of cells due to apoptosis, which is partially caused by activation of caspase-3, occurs in the LS during postnatal development, with regional differences. They also indicate that sex difference in caspase-3-independent apoptosis contributes to morphological sexual differentiation of the LSi.

Aging↗
PubMed1989

Development of sex differences in the response of spiny mouse pups to adult male odors.

Using a three-choice preference test, olfactory-mediated investigatory activity in response to adult male urine odor was examined in a precocially active rodent, the spiny mouse (Acomys cahirinus) aged between 3-26 days. Temporally related sex differences were seen in the time spent in the presence of the odors of father's or unfamiliar adult male's urine, or distilled (control) water. Neither male nor female pups discriminated between odors from the father and strange adult males. After the first olfactory test, when the pups were aged between four and six days, male pups strongly preferred to stay in the vicinity of urine odors of adult males, whereas female pups avoided odors of adult males and remained in the enclosure with the control odor source. To our knowledge this is the first time that such a behavioral sex difference related to olfaction has been shown to occur in young rodent pups. We suggest that the sexually dimorphic response of the pups is associated with the development of later sex differences in behavior.

Animals↗
PubMed2003

Two perspectives on the origin of sex differences in the brain.

Most sex differences in brain function are attributed to sex differences in the effects of gonadal secretions. In addition, however, male and female cells differ because of differential effects of sex chromosome genes expressed within the cells themselves. The latter conclusion comes from numerous studies in which sexual phenotype appears to be insensitive to the effects of sex hormones during development or cases in which sex differences develop before the onset of sex-specific patterns of gonadal secretions. Recently, mouse models have become available in which the genetic sex of brain cells is independent of the gonadal type (testes vs. ovaries), which allows a test of the role of sex chromosome genes in brain development. This paper reviews the evidence that genetic sex of brain cells influences their sexual phenotype, and critically discusses the relative advantages of various experimental approaches to study this effect.

Animals↗
PubMed2005

Sex difference in development of diabetes and cardiovascular disease on the way from obesity and metabolic syndrome.

AIM: The objective of this study was to investigate sex-specific differences existing on the way from (abdominal) obesity and metabolic syndrome (MS) to type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). METHODS: A population sample of 1974 men and women, representative of Turkish adults (mean age, 48 years), with normal glucose metabolism (GM) and free of CVD at baseline, was prospectively evaluated at a mean 4.1 years of follow-up. The term abnormal GM designated both DM and impaired fasting glucose (IFG). Metabolic syndrome was identified in 29% of men and 40% of women by the criteria of the National Cholesterol Education Program guidelines. Fatal and nonfatal CVD, diagnosed by clinical findings and Minnesota coding of resting electrocardiograms, developed in 121 subjects. RESULTS: The cohort was dichotomized by the presence or absence of MS and of obesity defined by a body mass index of 30 kg/m 2 or greater. Compared with the major female group with no obesity or MS, women with MS, regardless of the presence of obesity, predicted highly significantly the development of abnormal GM with relative risks exceeding 2, whereas no independent significant association was noted in men with MS. Similar divergence of sexes pertained to the prediction of diabetes. When age, smoking status, grade of physical activity, IFG, DM, and the 4 groups with obesity and MS were analyzed for the prediction of CVD by logistic regression, men with MS, regardless of the presence of obesity, predicted highly significantly CVD (with relative risks ranging from 2 to 4), but neither DM nor IFG contributed independently. Conversely, in women, abnormal GM predicted CVD independent of age, smoking status, and grade of physical activity, but the groups with obesity and MS failed to significantly contribute independently. CONCLUSIONS: In populations with prevalent MS, whereas women with normal GM are prone to DM within the context of MS and are exposed to CVD risk primarily by way of DM, men are prone to visceral adiposity, less susceptible to DM, and run CVD risk primarily by the intermediary of MS, largely independent of the DM component.

Cardiovascular Diseases↗
PubMed1984

Sex differences in development of fetal rat lung. II. Quantitative morphology of epithelial-mesenchymal interactions.

Mesenchymal factors are important in organ growth and differentiation and may affect epithelial function in the developing lung. In the present study, the role of epithelial-mesenchymal interactions in rat lung development is investigated by serial quantitative analysis of pulmonary ultrastructure. Because of sex-related differences in fetal pulmonary maturity, the formation of intercellular contacts is compared in male and female littermates grouped according to sex from day 17 to 22 of gestation. It was found that, as full term approached, continuity of the basement membrane under cuboidal epithelial cells decreased, the number of foot processes on these cells increased, and the percentage of processes that penetrated the basement membrane also increased. These changes occurred more rapidly in female animals. Intercellular contacts between epithelial and interstitial cells became more frequent with time and were observed more often in females at days 19 and 20. The incidence of cuboidal epithelial cells containing lamellar bodies was greater in females at day 20. No sex-related differences were found at day 22 in any parameter studied. The results demonstrate a correlation between the increasing frequency of epithelial-mesenchymal cell contacts and the onset of epithelial differentiation. Since these events occur earlier in females, it is postulated that androgen levels are important in regulating epithelial growth and differentiation in the developing lung.

Animals↗
PubMed2002

Development of sex differences in the rabbit masseter muscle is not restricted to a critical period.

The proportions of muscle fibers of different phenotype in the adult rabbit masseter differ greatly in different sexes. These sex differences are not apparent in young adults, but arise under the influence of testosterone in the males. We examined whether this switch occurred during a critical period of postnatal development. Testosterone was administered to young adults 1, 2, or 4 mo after castration, and also to adult females. Samples of masseter muscle were taken at four monthly intervals after the onset of treatment and examined for the expression of different myosin heavy chain (MyHC) isoforms by using a panel of monoclonal antibodies. Despite the length of androgen deprivation, treatment with testosterone produced a marked MyHC isoform switch from alpha-slow/beta to IIa. This male proportion of fibers of different phenotypes persisted well beyond the return of serum testosterone levels to pretreatment levels. Thus brief exposure to testosterone produces a permanent change in the proportions of masseter muscle fibers of different phenotypes, and the capacity for this change is not restricted to a critical period.

Animals↗
PubMed1997

Postnatal development and sex difference in neurons containing estrogen receptor-alpha immunoreactivity in the preoptic brain, the diencephalon, and the amygdala in the rat.

Estrogen has been considered as a key substance that induces sexual differentiation of the brain during fetal and neonatal life in the rat. Thus, to define the brain regions involved in the brain sexual differentiation, we examined the regions where the estrogen receptor (ER) is located in the developing rat brain. We examined immunohistochemical distribution of the cells containing estrogen receptor-alpha (ER-alpha) in the preoptic region, the diencephalon, and the amygdala in male and female rats on postnatal days 1-35 (PD1-PD35). The antibody used recognizes ER-alpha equally well for both occupied and unoccupied forms. ER-alpha immunostaining was restricted to the cell nuclei of specific cell groups. In PD1 rats, ER-alpha-immunoreactive (ER-IR) signals were detected in the lateral septum, the organum vasculosum lamina terminalis, the medial preoptic nucleus (MPN), the median preoptic nucleus, the bed nucleus of the stria terminalis, the hypothalamic periventricular nucleus, the lateral habenula, the posterodorsal part of the medial amygdala nucleus, the posterior part of the cortical amygdala nucleus, the hypothalamic ventromedial nucleus (VMH), the hypothalamic arcuate nucleus, and the posterior hypothalamic periventricular nucleus. The distribution pattern of ER-IR cells in the newborn rat was much the same as that in the adult in the preoptic-hypothalamic and amygdala regions. Moreover, the signals in the MPN and the VMH were stronger in the female than in the male, perhaps reflecting the ability ofestrogen generated by aromatization of testosterone in the male to down-regulate the ER signal. Thus, the brain regions showing sex differences may be sites of sexual differentiation of the brain by aromatizable androgen during the neonatal period.

Amygdala↗
PubMedDate not supplied

The role of gender-related processes in the development of sex differences in self-evaluation and depression.

This paper examines gender socialization processes during childhood that may contribute to a higher incidence of depression or depressive symptoms in females than in males. It is argued that because of the actions of socialization agents and the impact of gender stereotypes on a child's construction of gender identity, girls may exhibit higher levels of self-evaluative concerns that increase vulnerability to depression. Indeed, a review of the literature on sex differences in self-evaluation suggests that girls may be more susceptible than boys to self-evaluative concerns, particularly as reflected in lower expectations for future success, more maladaptive causal attributions for success or failure outcomes, and negative behavioral and evaluative reactions to failure. Moreover, an examination of the literature on sex differences in depressive symptoms leads to questions about previous conclusions that girls do not exhibit higher levels of depressive symptoms prior to adolescence. Finally, we present some recent original data that support the contention that sex differences in vulnerability to depression may be evident prior to adolescence.

Adolescent↗
PubMed1981

Postnatal development and sex differences in hepatic phosphatidate phosphohydrolase activity in the rat.

The mechanism leading to the difference in hepatic triacylglycerol metabolism between female and male rats was investigated by studying the ontogeny of hepatic soluble phosphatidate phosphohydrolase activity in feeding animals of both sexes. A sevenfold increase occurred within 12 hr of birth, returning to the adult level during the third postnatal day. The changes in enzyme activity were followed by similar changes in hepatic triacylglycerol concentrations. A sex difference was observed only in the adult rats, where the enzyme activity in the livers of feeding female rats was about 25% higher than that in the feeding males. The effects of gonadectomy and sex steroids were studied in a separate series of experiments on fasting animals. The activity of the soluble enzyme was 65% higher in the intact female rats than in the males, and that of the microsomal enzyme 130% higher. The activity ratio between the soluble and microsomal enzyme in the male rats was 4.3 on a liver wet weight basis with the methods used. Gonadectomy increased the soluble and microsomal activities by 25% and 80% respectively within 6 wk in the male rats. The soluble and microsomal activities were still at the same control levels 2 wk after the gonadectomy, the subcutaneous implants of testosterone or estradiol resulting in 10-fold increases in plasma hormone levels had no effects on these enzyme activities, although testosterone caused 50% decrease in the hepatic triacylglycerol concentration. These data indicate that, if hormonally mediated, the postnatal increase in phosphatidate phosphohydrolase activities is not related to sex steroids and also suggest that the basis of the sex difference in hepatic soluble phosphatidate phosphohydrolase activity remains to be established.

Aging↗