Gonadal hormones influence the emergence of cortical function in nonhuman primates.

The role of gonadal hormones in the maturation of the orbital prefrontal cortex (ORB) was studied in normal male and female rhesus monkeys, monkeys given ORB lesions at 50 days of age, and female monkeys given androgen at different ages. Monkeys were tested on an object discrimination reversal task at 75 days of age. Gender influenced the performance of monkeys on the task during normal development and after ORB lesions. Normal males made fewer errors than did normal females. Females treated with androgen performed similarly to normal male monkeys. ORB lesions produced deficits in male monkeys and in females given androgen during late prenatal or early postnatal life, but not in normal females. These findings suggest that gonadal hormones may play an inductive role in the differentiation of higher cortical function in nonhuman primates. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Early androgen effects on aggression in children and adults with congenital adrenal hyperplasia

Males are more likely than females to show aggressive behavior across species, ages, and situations, and these differences may be partly influenced by early hormones. We studied aggression in three samples of subjects with congenital adrenal hyperplasia (CAH), who were exposed to high levels of androgen in the prenatal and early postnatal periods. Controls were siblings and first cousins similar in age. In Sample 1, adolescents and adults completed the Multidimensional Personality Questionnaire (MPQ), which includes an Aggression scale. In Sample 2, adolescents and adults completed the MPQ and a paper-and-pencil version of Reinisch's Aggression Inventory. In Sample 3, parents rated the aggression of children aged 3-12, using a modification of Reinisch's Inventory. In all three samples, control males had higher aggression scores than control females. Further, as predicted, females with CAH had higher aggression than control females, but the difference was significant only in adolescents and adults. These results suggest that early androgens contribute to variability in human aggression.     

Neonatal androgenic stimulation and adult sexual behavior in male and female golden hamsters.

In an experiment with 48 male and 48 female golden hamsters, neonatally and adult castrated males as well as neonatally androgenized and nonandrogenized females were tested for both mounting and lordosis behaviors during treatment with either testosterone or ovarian hormones. Neonatal androgenization facilitated mounting behavior in adult Ss administered either testosterone or ovarian hormones and suppressed lordosis behavior in adult ovarian-hormone-treated Ss. Early androgen effects on the display of lordosis behavior during adult testosterone treatment were complex and varied with the exact timing of perinatal endogenous or exogenous androgenization. Species differences in hormone-behavior relationships and the possible role of perinatal androgenization in the development of rodents' ability to aromatize androgens are discussed. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Activating effects of androgens on cognitive performance: causal evidence in a group of female-to-male transsexuals

It is still unclear whether sex differences in cognitive functioning are mainly due to perinatal organizing effects of sex hormones on the brain, or to activating effects in adulthood. In a group of 22 female-to-male transsexuals a battery of visuospatial and verbal ability tests was administered twice: shortly before and 3 months after the start of androgen treatment. The administering of androgens was clearly associated with an increase in spatial ability performance. In contrast, it had a deteriorating effect on verbal fluency tasks. This study offers preliminary evidence that androgens directly and quickly affect cognitive performance in females.     

Sexual differentiation of the vertebrate brain: principles and mechanisms

A wide variety of sexual dimorphisms, structural differences between the sexes, have been described in the brains of many vertebrate species, including humans. In animal models of neural sexual dimorphism, gonadal steroid hormones, specifically androgens, play a crucial role in engendering these differences by masculinizing the nervous system of males. Usually, the androgen must act early in life, often during the fetal period to masculinize the nervous system and behavior. However, there are a few examples of androgen, in adulthood, masculinizing both the structure of the nervous system and behavior. In the modal pattern, androgens are required both during development and adulthood to fully masculinize brain structure and behavior. In rodent models of neural sexual dimorphism, it is often the aromatized metabolites of androgen, i.e., estrogens, which interact with estrogen receptors to masculinize the brain, but there is little evidence that aromatized metabolites of androgen play this role in primates, including humans. There are other animal models where androgens themselves masculinize the nervous system through interaction with androgen receptors. In the course of masculinizing the nervous system, steroids can affect a wide variety of cellular mechanisms, including neurogenesis, cell death, cell migration, synapse formation, synapse elimination, and cell differentiation. In animal models, there are no known examples where only a single neural center displays sexual dimorphism. Rather, each case of sexual dimorphism seems to be part of a distributed network of sexually dimorphic neuronal populations which normally interact with each other. Finally, there is ample evidence of sexual dimorphism in the human brain, as sex differences in behavior would require, but there has not yet been any definitive proof that steroids acting early in development directly masculinize the human brain.     

Calorie restriction lowers body temperature in rhesus monkeys, consistent with a postulated anti-aging mechanism in rodents

Many studies of caloric restriction (CR) in rodents and lower animals indicate that this nutritional manipulation retards aging processes, as evidenced by increased longevity, reduced pathology, and maintenance of physiological function in a more youthful state. The anti-aging effects of CR are believed to relate, at least in part, to changes in energy metabolism. We are attempting to determine whether similar effects occur in response to CR in nonhuman primates. Core (rectal) body temperature decreased progressively with age from 2 to 30 years in rhesus monkeys fed ad lib (controls) and is reduced by approximately 0.5 degrees C in age-matched monkeys subjected to 6 years of a 30% reduction in caloric intake. A short-term (1 month) 30% restriction of 2.5-year-old monkeys lowered subcutaneous body temperature by 1.0 degrees C. Indirect calorimetry showed that 24-hr energy expenditure was reduced by approximately 24% during short-term CR. The temporal association between reduced body temperature and energy expenditure suggests that reductions in body temperature relate to the induction of an energy conservation mechanism during CR. These reductions in body temperature and energy expenditure are consistent with findings in rodent studies in which aging rate was retarded by CR, now strengthening the possibility that CR may exert beneficial effects in primates analogous to those observed in rodents.     

Effects of neonatal RU486 on adult sexual, parental, and fearful behaviors in rats.

Exposure to gonadal hormones during perinatal life influences later behavior. The finding that sex differences exist in progestin receptor expression in the perinatal rat brain suggests differential sensitivity of male and female brains to progesterone (C. K. Wagner, A. N. Nakayama, & G. J. De Vries, 1998). Because these sex differences are in neural sites that influence sexually differentiated sexual, parental, and fearful behaviors in adults, this study examined the effects of administering the progestin receptor antagonist RU486 for the first 10 days after birth on these behaviors in adulthood. Neonatal RU486 significantly reduced sexual behavior in males but did not impair reproduction in females. Neonatal RU486 did not affect parental responses of virgin rats exposed to pups (sensitization) but reduced fear in the elevated plus-maze in both sexes. Treatment of pups with RU486 affected neither mother–litter interactions nor plasma testosterone levels in males during or after treatment. These results suggest that neonatal exposure to progesterone, in addition to androgens and estrogens, influences behavioral development in rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

DNA-protein interactions in the proximal zeta-globin promoter: identification of novel CCACCC- and CCAAT-binding proteins

The present study assessed whether prenatal androgen and estrogen exposure affected adult spatial learning and hippocampal morphology. Water maze performance, the CA1 and CA3 pyramidal cell field, and the dentate gyrus-granule cell layer (DG-GCL) morphology were assessed at adulthood (70+ days of age) in males, females, androgen-treated (testosterone propionate, TP, or dihydrotestosterone propionate, DHTP) females (2-4 mg/day), estradiol benzoate (EB)-treated females (100 microgram/day), and males treated with the antiandrogen flutamide (8 mg/day). Pregnant rats were injected daily (sc) between Embryonic Day 16 and birth; all pups were delivered by cesarean section. Flutamide-treated males were castrated upon delivery, and adult castrates were used to control for activational effects. Steroid-sensitive sex differences were observed in water maze performance in favor of males. Males had larger CA1 and CA3 pyramidal cell field volumes and soma sizes than females, which were feminized with flutamide treatment. TP and EB, but not DHTP, masculinized CA1 pyramidal cell field volume and neuronal soma size; CA3 was masculinized in both TP- and DHTP-treated females, while EB was ineffective. No effects were observed in cell density, number, or DG-GCL volume or due to adult hormone levels. Thus, prenatal androgens and estrogen influence sex differences in adult spatial navigation and exert differential effects on CA1 and CA3 pyramidal cell morphology. Hence, in addition to the previously reported postnatal component, there is also a prenatal component to the critical period in which gonadal steroids organize the neural mechanisms underlying sex differences in adult spatial ability.     

Prenatal and neonatal androgen exposure interact to affect sexual differentiation in female rats.

Rats were injected with oil on Days 17.5 and 18.5 of pregnancy or with 2 mg of testosterone propionate (TP) on Days 15.5 and 16.5, or Days 17.5 and 18.5, or Days 19.5 and 20.5. The female offspring were given oil or 5 μg of TP on Day 25 postconception. Among females exposed to TP only during prenatal ontogeny, a lower proportion of those treated on Days 17.5–28.5 of gestation displayed lordotic behavior than did the control group. Postnatal TP alone did not affect lordosis. However, all groups receiving combined pre- and postnatal TP showed impaired estrous patterns. The development of several components of morphology also was differentially affected by the timing of the androgen exposure. The data suggest that the differentiation of sexual behavior and reproductive morphology in the rat are influenced by an interaction of androgen dependent processes operating at different stages of perinatal ontogeny. Further, there may be an optimal fetal period during which androgenization sensitizes animals to low levels of testosterone circulating during neonatal development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive gender differences in very young children parallel biologically based cognitive gender differences in monkeys.

Infant humans were trained on 2 cognitive tests that have previously revealed, in infant monkeys, a double dissociation that was reversible by perinatal manipulations of androgens and ablations of specific brain sites. Children showed the same sex-linked behavior found with infant monkeys: young boys were superior on the object reversal task and young girls were superior on the concurrent discrimination task. As happened previously with infant monkeys, the gender difference was not apparent in older human subjects. Thus, early in ontogeny, cognitive gender differences have now been discovered in both humans and monkeys, probably a result of gender differences in androgens that influence the maturation rate of specific brain systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Androgen effects on women's gendered behaviour

Test of the applicability of the hormonal theory of sex-dimorphic behaviour to adult women is achieved in this study by assembling measures of prenatal and adult androgen exposure, and a broad measure of gendered behaviour on a sample of white women aged 27-30. Androgen exposure in the second (and no other) trimester of fetal life, combined with and in interaction with adult androgens, masculineses women's behaviour and explains a substantial proportion of the within-sex variance in women's adult gendered behaviour.     

Dietary phytoestrogens dampen female sexual behavior in mice with a disrupted aromatase enzyme gene.

Aromatization of testosterone (T) to estradiol (E2) during perinatal development in male rodents plays a significant role in sexual differentiation of the brain and adult behaviors. Exposure to estrogens during development can enhance masculine behaviors in adult females and reduce expression of female-typical behaviors in adult males. Previous studies have shown that, in addition to naturally occurring estrogens, dietary phytoestrogens can affect sexual differentiation. To distinguish between the effects of endogenous T-derived E2 and exogenous phytoestrogens, the authors used an aromatase knockout (ArKO) mouse that cannot produce E2 but is responsive to E2 via estrogen receptors α and β. Dams and their litters were maintained either on a standard mouse chow that was rich in phytoestrogens or on a chow nearly devoid of phytoestrogens. Mice were maintained on their perinatal diets after weaning. Adults of both sexes were gonadectomized and tested for lordosis behavior. In the ArKO females raised on a diet high in phytoestrogens, lordosis was reduced in comparison with females of both genotypes on the low phytoestrogen diet. The authors' findings suggest that dietary phytoestrogen consumption may partially defeminize adult female sexual behavior in the mouse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Social play soliciting by male and female juvenile rats: Effects of neonatal androgenization and sex of cagemates.

Investigated the behavior of male and female Long-Evans hooded rats during individual exposure to nonplayful juvenile social stimuli in a novel test of play-soliciting behavior in 2 experiments examining hormonal and experiential determinants of sex differences. In Exp I, using 36 female and 18 male Ss, neonatally androgenized females engaged in play soliciting at a level equal to that of male controls and greater than that of nonandrogenized female controls. In Exp II, 52 males and 32 females were reared in unisexual and bisexual groups in order to compare long-term sex-related social experience effects on juvenile play soliciting. Males exposed only to other young males engaged in greater play soliciting than males exposed to both sexes; females, in contrast, were unaffected by sex of cagemates. Within rearing conditions, however, males engaged in greater play soliciting than females. The combined results suggest that perinatal gonadal androgen exposure effects on social play are prepotent and contribute essentially to sex differences in the initiation of social play behavior. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hormone therapy in advanced and generalized carcinoma of the prostate]

The prostate grows and functions within a multihormonal environment. It consists of androgens, oestrogens, gonadotrophins, gonadotrophin-releasing hormones and gestagens. Growth factors are produced under the influence of androgen stimulation. We show all possibilities of androgen deprivation of advanced and metastatic prostate cancer.     

A neuroanatomical correlate of paternal and maternal behavior in the biparental California mouse (Peromyscus californicus).

The medial preoptic area (MOPA) is important in the control of maternal behavior in rodents, and it is sexually dimorphic. This study demonstrates that the MPOA of 10 nonparental virgin male Peromyscus californicus was larger than that of 9 virgin females because of a significantly greater number of neurons in the MPOA of virgin males. However, this sex difference in MPOA volume disappeared when males and females became parents. Soma size increased significantly when females became mothers. These data suggest that maternal behavior may require a structural change in the MPOA, whereas paternal responsivity, which is normally inhibited in virgin males, may require a change in neuronal activity. Furthermore, these results underscore the importance of reproductive status in examination of sexually dimorphic nuclear structures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of gender and the endocrine environment on the distribution of androgen receptors in the lacrimal gland

Androgens are known to regulate both the structure and function of lacrimal tissue in a variety of species. To explore the endocrine basis for this hormone action, the following study was designed to: (1) determine the cellular distribution of androgen receptors in the lacrimal gland; and (2) examine the influence of gender and the endocrine environment on the glandular content of these binding sites. Lacrimal glands were obtained from intact, castrated, hypophysectomized, diabetic or sham-operated male or female adult rats, mice or hamsters, as well as from orchiectomized rats exposed to placebo compounds or physiological levels of testosterone. The cellular location of androgen receptors was evaluated by utilizing an immunoperoxidase protocol, in which a purified rabbit polyclonal antibody to the rat androgen receptor was used as the first antibody. Our findings with lacrimal glands showed that: (1) androgen receptors are located almost exclusively in nuclei of epithelial cells; (2) the cellular distribution or intranuclear density of these binding sites is far more extensive in glands of males, as compared to females; (3) orchiectomy or hypophysectomy, but not sham-surgery or diabetes, lead to a dramatic reduction in the immunocytochemical expression of androgen receptors; and (4) testosterone administration to orchiectomized rats induces a marked increase in androgen receptor content, relative to that in placebo-exposed glands. Our results also reveal that a 10 kb androgen receptor mRNA exists in the rat lacrimal gland. Overall, these findings demonstrate that gender and the endocrine system may significantly influence the distribution of androgen binding sites in rat lacrimal tissue. Moreover, our results show that androgens up-regulate their own lacrimal gland receptors.     

Prenatal and perinatal influences on risk for psychopathology in childhood and adolescence

The relationship between a range of prenatal and perinatal events and risk for psychopathology in offspring was examined. Prenatal and perinatal events investigated included maternal experiences, health, and substance use during pregnancy, obstetric complications, feeding practices, and infant health during the first year of life. Offspring diagnosis was based on structured interviews conducted with 579 adolescents on two occasions. Risk for later psychopathology was associated with a number of prenatal and perinatal factors. Major depression was associated with not being breast fed and maternal emotional problems during the pregnancy. Anxiety was chiefly associated with fever and illness during the first year of life and maternal history of miscarriage and stillbirth. Disruptive behavior disorder was associated with poor maternal emotional health during the pregnancy and birth complications. Risk for substance use disorder was associated with maternal use of substances during the pregnancy. Mediating effects of maternal depression, maternal-child conflict, and physical symptoms in the child, and moderating effects of gender of child and parental education were also evaluated. The limitations of this study are discussed and future research directions are suggested.     

Androgens and the organization of sex differences in active avoidance behavior in the rat.

Performed 3 experiments to clarify the role of androgens in the development of sex differences in the acquisition of active avoidance behavior in a total of 248 male and 231 female Holtzman albino rats. Gonadectomy in adulthood did not affect the performance of either sex regardless of the length of the postoperative recovery interval. Neonatal castration also failed to improve the avoidance performance of males, but prenatal exposure to the antiandrogen cyproterone acetate combined with neonatal gonadectomy produced males whose avoidance acquisition and open field activity scores were indistinguishable from those of control females. Prenatal exposure to endogenous androgens was sufficient to organize the avoidance behavior characteristic of normal males, but there is no compelling evidence that exposure to androgens during the prenatal period was critical to this effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Feminine dimension in the play fighting of rats (Rattus norvegicus) and its defeminization neonatally by androgens.

In rats, juvenile males engage in more play fighting (a male-typical behavior) than do juvenile females, and this difference is based on perinatal influences of androgens. The authors show that there are qualitative and quantitative differences between the sexes in the type of defensive responses and their manner of execution. In defensive responses, rats try to avoid having their napes contacted by their partner's snout. The sex differences arise from females' greater response distance; that is, females responded to an approach when the partner's snout was further from the nape. This permits females to use different defensive responses and to use them more successfully. This greater response distance is defeminized by the neonatal administration of testosterone propionate. Findings suggest that play fighting in rats has both male- and female-typical features and that these are, at least in part, influenced perinatally by androgens. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term effects of prenatal stress and handling on metabolic parameters: relationship to corticosterone secretion response

The prenatal and postnatal environment exerts a long-term influence on the stress-response of the hypothalamic-pituitary-adrenal (HPA) axis. In this study, the long-term effects of prenatal and postnatal manipulations and their related changes on glucocorticoid secretion were examined on metabolic parameters in adult rats. Plasma glucose levels, body weight and basal feeding behavior were measured. We show that modifications of the prenatal and postnatal environment have opposite long-term effects on these parameters, except for blood glucose, which was increased in prenatally stressed animals. Although the mechanisms underlying these phenomena remain to be elucidated, the observations show that perinatal manipulations have long-term effects on metabolic functions related to HPA activity.