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PubMed1994

Female pseudohermaphroditism with multiple caudal anomalies: absence of Y-specific DNA sequences as pathogenetic factors.

46,XX female pseudohermaphrodites have been previously described with nearly complete masculinization of the external genitalia and no apparent source of testosterone. Multiple malformations of internal genital, urinary, and gastrointestinal tracts are associated. We have evaluated four such infants with female pseudohermaphroditism and multiple caudal anomalies. Three cases had apparently normal chromosomes (46,XX); one had a 46,XX,del(10)(q25.3-->qter) chromosome constitution. The chromosome breakpoint is in the region of PAX2, a developmentally important paired box gene which is expressed in urogenital tissue. Using the polymerase chain reaction, we screened for the presence of multiple Y specific sequences, including SRY (sex determining region, Y chromosome), that could explain masculinization of the external genitalia. All were negative for Y centromeric sequences, ZFY (Zinc finger Y), and SRY. Furthermore, there was no evidence for adrenal or other sources of testosterone. We suggest that the masculinization in these cases is the result of abnormal expression of genes which would normally be regulated by testosterone.

Abnormalities, Multiple↗
PubMed2004

Expression of androgen receptor mRNA in zebra finch song system: developmental regulation by estrogen.

By using improved methods for in situ hybridization to detect expression of androgen receptor (AR) mRNA, the distribution of expression was mapped in the adult male zebra finch brain. In the neural song circuit, robust expression was found in area X of the lobus parolfactorius (LPO) as well as in other song regions previously reported. Expression was also found in many areas of the hypothalamus and dorsal thalamic nuclei, nucleus intercollicularis and ventricular areas of the midbrain, cerebellar Purkinje and granule cells, the hyperstriatum, medial neostriatum, medial LPO, and archistriatum. In juvenile males, AR mRNA expression was first detected in nucleus high vocal center (HVC) at posthatch day 9 (P9), in area X at P9-P11, and in the region of the robust nucleus (RA) in the medial archistriatum by P7. Estrogen treatment of hatchling females caused an increase in the expression of AR mRNA in HVC and area X by P11, whereas treatment of hatchling males with the aromatase inhibitor fadrozole decreased the expression of AR mRNA at P11. The present results indicate that masculine development of AR expression begins in area X and HVC before they are thought to be synaptically connected, suggesting that different song nuclei initiate sexual differentiation independently of transsynaptic masculinizing influences. The present results suggest that estrogen is necessary for full masculine AR expression in the song system and that the estrogenic regulation of AR contributes to subsequent differential actions of androgen in male and female song nuclei.

Animals↗
PubMed1987

Sexual differentiation of androgen accumulation within the zebra finch brain through selective cell loss and addition.

In zebra finches males, but not females, respond to gonadal androgens with the production of a stereotyped courtship song. Corresponding to this dimorphism in hormone sensitivity, two song-related neural regions, magnocellular nucleus of the anterior neostriatum (MAN) and hyperstriatum ventralis pars caudalis (HVc), have more cells that accumulate androgens in males than in females. The early hormonal environment establishes these sex differences in the brain and behavior such that females treated with estradiol (E2) shortly after hatching have male-typical levels of androgen accumulation in MAN and HVc, and respond to adult androgen stimulation with male-typical song. Using autoradiographic procedures employing the androgen 3[H]-dihydrotestosterone (DHT), the present study focused on whether E2 masculinizes androgen target cell numbers in MAN and HVc by inducing, or rather preserving, a male-typical number of androgen target cells. First, it was demonstrated that E2 treatment of females as late as 20 days after hatching increases the number of MAN and HVc cells accumulating 3[H]-DHT or its metabolites in adulthood to levels typical of males. Then the number of androgen target cells present within these nuclei in 20-day-old females was compared with the number present in adult females previously masculinized with E2 treatment on day 20. In MAN, E2 masculinizes androgen accumulation by preserving androgen target cell numbers in the face of massive overall cell loss, a result that suggests that E2 promotes the survival of androgen target cells during sexual differentiation. In HVc, however, E2 treatment on day 20 promotes an addition of androgen target cells, suggesting that during adolescence, E2 regulates the proliferation, migration, and/or survival of these cells.

Animals↗
PubMed1989

Hormonal control of neuron number in sexually dimorphic spinal nuclei of the rat: III. Differential effects of the androgen dihydrotestosterone.

The spinal cord of the rat contains two sexually dimorphic nuclei: the spinal nucleus of the bulbocavernosus (SNB) and the dorsolateral nucleus (DLN). These nuclei and the perineal muscles they innervate are present in males but reduced or absent in females. The sex difference in motoneuron number in these nuclei is due to an androgen-regulated motoneuron death. Developing females treated with the androgen testosterone propionate (TP) have a fully masculine number of SNB and DLN motoneurons and retain the perineal muscles they would normally have lost. Paradoxically, females treated prenatally with the androgen dihydrotestosterone propionate (DHTP) also retain the perineal musculature but as adults lack the SNB motoneurons which would normally innervate them. The SNB target muscles retained by DHTP females are anomalously innervated by motoneurons in the DLN. Counts of motoneurons and degenerating cells in the developing SNB of DHTP-treated females showed that their feminine number is the result of a failure of DHTP to prevent the death of SNB motoneurons. Furthermore, the peak number of SNB motoneurons was below that of normal females, suggesting that DHTP treatment may also have inhibited motoneuronal migration. However, DHTP treatment fully masculinized both motoneuron number and degenerating cell counts in the DLN of these females, and it is this masculinized DLN that gives rise to the anomalous projection. Taken together, these results suggest that the effects of different androgens during development are specific and complex, involving the regulation of motoneuron death, migration, and specification of peripheral projections.

Aging↗
PubMed2005

Sex differences in juvenile rhesus macaque (Macaca mulatta) agonistic screams: life history differences and effects of prenatal androgens.

This study investigated sex differences in juvenile rhesus macaque (Macaca mulatta) vocal behavior during agonistic contexts, and the effects of prenatal androgens on these differences. A total of 59 subjects (5-8 per treatment group) received exogenous androgen (testosterone enanthate), an anti-androgen (flutamide) or vehicle injections (DMSO) for 30 or 35 days during the second (early) or third (late) trimester of pregnancy. An additional 19 unmanipulated controls were included in the analysis. Screams by juvenile males and females between the ages of 1 and 3 years were compared to the screams of adult female exemplars using a discriminant function analysis. Juvenile females produced more adult-female like screams than did juvenile males. Females exposed to androgen treatment late in gestation produced a more masculine pattern of screams. Flutamide treatment in males either early or late in gestation did not significantly affect scream production. Flutamide treatments in females late in gestation, however, masculinized scream production. Androgen treatments administered late in gestation hyper-masculinized male scream production. No sex differences in the contextual usage of screams emerged. These findings suggest that both life history differences and the early hormone environment contribute to sex differences in juvenile rhesus macaque vocal production.

Agonistic Behavior↗
PubMed1979

Neonatal treatment of hamsters with barbiturate alters adult sexual behavior.

Male and female hamsters were given 50 micrograms pentobarbital, 100 micrograms pentobarbital, or 100 micrograms d-amphetamine on postnatal Days 2-4. When tested for masculine sexual behavior in adulthood, males treated with 100 micrograms pentobarbital showed behavioral deficits when tested with testes intact as well as after castration and treatment with testosterone propionate. Deficits shown by 50 micrograms pentobarbital males were overcome by testosterone replacement. When tested for feminine sexual behavior, males treated with 50 micrograms pentobarbital showed enhanced lordotic responses whereas males treated with 100 micrograms d-amphetamine showed no differences from controls when tested for female sexual behavior or when tested for male sexual behavior. Drug treatments had no effect on adult masculine or feminine sexual behavior in neonatally treated females. The results of this study show that pentobarbital can inhibit normal masculinization of the male when given during behavioral sexual differentiation.

Animals↗
PubMedDate not supplied

Autologous tunica vaginalis and subcapsular orchiectomy: a hormonal therapy for prostate cancer.

Two novel surgical procedures that combine an autologous tunica vaginalis pedicle graft (TVG) with a subcapsular orchiectomy (SCOT) were evaluated in asymptomatic patients with rising prostate-specific antigen (PSA) values following radiation therapy, a radical retropubic prostatectomy, or a newly diagnosed prostatic cancer with bony metastasis. In the SCOT I procedure, the TVG was secured to the inner wall of the tunica albuginea. In the SCOT II procedure, the TVG was folded and secured to the external wall of the tunica albuginea. Between December 1, 1999, and July 1, 2000, 26 patients were offered hormonal therapy. Twelve patients selected the SCOT I procedure, 12 selected a luteinizing hormone-releasing hormone (LHRH) agonist, and 2 selected a bilateral total orchiectomy (BTO). Because the cosmetic outcome of the SCOT I procedure was less than ideal, this procedure was modified in December 2001. Between December 1, 2001, and July 1, 2002, 28 hormonal candidates were evaluated. Twelve patients selected the SCOT II procedure, 11 selected an LHRH agonist, and 5 selected a BTO. Preoperative measurements of the testicular area and PSA were obtained. During postoperative visits, the total testosterone, PSA, and testicular area were determined, and the Fugl-Meyer questionnaire (FMQ) and SCOT-specific questionnaire (SSQ) were completed. Between March 1, 2000, and December 1, 2002, 10 patients underwent a BTO. This group was the control for the postoperative SCOT total testosterone values. Sixty-three percent of the mean preoperative testicular area was preserved in the SCOT II group vs 43% in the SCOT I group at the 9- to 12-month visit (P <.01). The mean postoperative total testosterone values for the SCOT I, SCOT II, and BTO groups were in the castrate range. No statistically significant difference was noted between the preoperative and postoperative FMQ scores among the SCOT I and SCOT II groups. Eighty-three percent of the SCOT II patients experienced no change in masculine identity, and 58% noted no change in testicular size. One hundred percent of the SCOT I patients experienced no change in masculine identity and noted no change in testicular size. The SCOT II procedure preserved a greater testicular area than the SCOT I. Both SCOT procedures achieved castrate levels of total testosterone and maintained masculine identity in 83%-100% of patients.

Aged↗
PubMed2005

Evidence-based assessment with men.

Men are almost universally underrepresented in psychological clinics and practices in the United States. One possible explanation for this underrepresentation is that men frequently conceal or obscure their emotional difficulties as a consequence of masculine gender role socialization. Men who subscribe to traditional, Western masculine values may be inclined to hide, minimize, or otherwise have difficulty expressing their psychological suffering, rendering this suffering difficult for clinicians to observe, diagnose, and treat. This manuscript describes an approach to the assessment process with men that integrates clinical reports on assessment and psychotherapy with men, values pertaining to our culture's construction of traditional masculinity, and empirical findings on psychological disorders more commonly observed in men.

Evidence-Based Medicine↗
PubMed2005

Men and therapy: critical concepts, theoretical frameworks, and research recommendations.

Scholars are increasingly recognizing the existence of multiple evolving conceptions of masculinity and the need for psychologists to better attend to masculinity-related constructs and their implications for men's lives. This article seeks to respond to this need by (a) reviewing research linking masculinity-related constructs to clinically relevant issues, (b) providing suggestions for building effective therapeutic relationships with male clients, (c) describing the role that culture and racism may play in male clients' lives, and (d) offering recommendations for future research.

Adolescent↗
PubMed2001

Aromatase plays a key role during normal and temperature-induced sex differentiation of tilapia Oreochromis niloticus.

In the tilapia Oreochromis niloticus, sex is determined genetically (GSD), by temperature (TSD) or by temperature/genotype interactions. Functional masculinization can be achieved by applying high rearing temperatures during a critical period of sex differentiation. Estrogens play an important role in female differentiation of non-mammalian vertebrates. The involvement of aromatase, was assessed during the natural (genetic all-females and all-males at 27 degrees C) and temperature-induced sex differentiation of tilapia (genetic all-females at 35 degrees C). Gonads were dissected between 486--702 degree x days. Aromatase gene expression was analyzed by virtual northern and semi-quantitative RT-PCR revealing a strong expression during normal ovarian differentiation concomitant with high levels (465 +/- 137 fg/g) of oestradiol-17 beta (E2-17 beta). This was encountered in gonads after the onset of ovarian differentiation (proliferation of both stromal and germ cells prior to ovarian meiosis). Genetic males exhibited lower levels of aromatase gene expression and E2-17 beta quantities (71 +/- 23 fg/ g). Aromatase enzyme activity in fry heads established a sexual dimorphism in the brain, with high activity in females (377.9 pmol/head/hr) and low activity in males (221.53 pmol/head/hr). Temperature induced the masculinization of genetic females to a different degree in each progeny, but in all cases repression of aromatase expression was encountered. Genetic males at 35 degrees C also exhibited a repression of aromatase expression. Aromatase brain activity decreased by nearly three-fold in the temperature-masculinized females with also a reduction observed in genetic males at 35 degrees C. This suggests that aromatase repression is required in the gonad (and perhaps in the brain) in order to drive differentiation towards testis development. Mol. Reprod. Dev. 59:265-276, 2001.

Animals↗
PubMed2001

Ovariectomy attenuates dendritic growth in hormone-sensitive spinal motoneurons.

The lumbar spinal cord of rats contains the sexually dimorphic, steroid-sensitive spinal nucleus of the bulbocavernosus (SNB). Dendritic development of SNB motoneurons in male rats is biphasic, initially showing exuberant growth through 4 weeks of age followed by a retraction to mature lengths by 7 weeks of age. The initial growth is steroid dependent, attenuated by castration or aromatase inhibition, and supported by hormone replacement. Dendritic retraction is also steroid sensitive and can be prevented by testosterone treatment, but is unaffected by aromatase inhibition. Together, these results suggest a role for estrogens during the initial growth phase of SNB development. In this study, we tested whether ovarian hormones could support SNB somal and dendritic development. Motoneuron morphology was assessed in normal males and in females perinatally masculinized with dihydrotestosterone and then either ovariectomized or left intact. SNB motoneurons were retrogradely labeled with cholera toxin-HRP at 4 or 7 weeks of age and reconstructed in three dimensions. Initial growth of SNB dendrites was reduced after ovariectomy in masculinized females. However, no differences in dendritic length were seen at 7 weeks of age between intact and ovariectomized masculinized females, and lengths in both groups were significantly lower than those of normal males. Together with previous findings, these results suggest that estrogens are involved in the early growth of SNB dendrites, but not in their subsequent retraction.

Animals↗
PubMed1994

Sexual differentiation of brain and behavior in the zebra finch: critical periods for effects of early estrogen treatment.

In order to determine the critical period(s) during which estrogen alters sexually dimorphic behavior and neuroanatomy in zebra finches (Poephila guttata), nestlings were injected daily with 20 micrograms estradiol benzoate (EB) during posthatching week 1, week 2, week 3, or weeks 1, 2, and 3. At 7 months of age, birds were implanted with testosterone propionate and tested with female partners for singing, dancing, and copulatory mounting. Brains were subsequently processed for morphometry, and the volumes of the song system nuclei HVC, area X, and RA and the soma sizes and densities of neurons in RA were determined. Males given EB during week 1 failed to mount. Females given EB during week 1 were fully masculinized with respect to dancing and RA neuron soma size and density, and were partially masculinized with respect to song nuclei volumes and singing. Treatment beginning after week 1 was ineffective or less effective for all measures. Only for RA neuron measures was treatment for all three weeks more effective than week 1 treatment. Thus the first post-hatching week is the most influential period of those tested for effects of exogenous estrogen on sexual differentiation in this species, and is a period during which both masculinization of females and demasculinization of males is possible.

Animals↗
PubMed1993

Effects of natural, synthetic, aromatizable, and nonaromatizable androgens in inducing male sex differentiation in genotypic female chinook salmon (Oncorhynchus tshawytscha).

The relative potency of several androgens to induce the male phenotype in sexually undifferentiated genotypic female chinook salmon were compared in two separate experiments. The aromatizable and nonaromatizable androgens testosterone (T) and 11-ketotestosterone (11-KT), and the synthetic aromatizable and nonaromatizable androgens 17 alpha-methyltestosterone (MT) and 17 alpha-methyldihydrotestosterone (MDHT) were administered to newly hatched alevins in a single 2-hr immersion treatment at doses ranging from 3.2 micrograms/liter to 10 mg/liter. The influence of these treatments on sex differentiation was evaluated by the histological examination of the resulting gonads 6 and 11 months later. In the control group, which was not exposed to exogenous steroids, no males or intersex fish were observed. In contrast, essentially 100% masculinization occurred in groups exposed to MDHT at dosages of 400 micrograms/liter and higher. Treatment with the aromatizable androgen MT resulted in a dose-dependent masculinization, with the production of 100% males at 400 micrograms/liter. However, higher doses resulted in fewer males. 11-KT and T were less potent than the synthetic androgens. The number of males produced after treatment with 11-KT followed a dose-dependent pattern while T showed virtually no masculinizing effect in inducing male phenotype in these studies. The resultant AD50 dosage levels (dosage at which 50% of the genotypic females were sex-reversed into phenotypic males) after a single 2-hr immersion treatment were: 30, 60, and 500 micrograms/liter for MDHT, MT, and 11-KT, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗
PubMed1998

Sex reversal by implantations of ethanol-treated androgenic glands of female isopods, Armadillidium vulgare (Malacostraca, crustacea).

The androgenic glands (AGs) of malacostracan crustaceans are responsible for differentiation of male sexual characteristics, and sex reversal is readily obtained by implantation of AGs in female crustaceans. In order to induce sex reversal, we implanted inactive AGs (dead cells) into young females of Armadillidium vulgare. Before implantation fresh AGs (living cells) were treated twice with 80% ethanol for 3 min and kept in crustacean physiological saline for 30 s. We refer to these AGs as ethanol-treated AGs (t-AGs). Stage 6 females were used as recipients of t-AG implantation. They received an implant of three t-AGs (3 t-AGs) three times, once each week. Testis formation in recipients was used as an indicator of the masculinized levels of female gonads. Female sexual characteristics were masculinized in proportion to the number of 3 t-AG implantations. Three implantations (total number of t-AGs, nine glands) induced development of testes, penes, and male copulatory organs in the recipient females. Furthermore, they could produce progeny. These results show that t-AG implantations are capable of inducing masculinization of female sexual characteristics. The procedure of three implantations with 3 t-AGs at stage 6 is enough to transform the sex from a genetic female into a functional male. If t-AGs are used to implant instead of fresh AGs, we can detect the effects induced by newly formed AGs of recipient females, not by implanted donor's AGs. The present method may be useful for examining the regulatory mechanism of sex differentiation of female A. vulgare.

Androgens↗
PubMed2002

Prenatal stress and gender role behavior in girls and boys: a longitudinal, population study.

Prenatal stress influences neural and behavioral sexual differentiation in rodents. Male offspring of stressed pregnancies show reduced masculine-typical characteristics and increased feminine-typical characteristics, whereas female offspring show the opposite pattern, reduced feminine-typical and increased masculine-typical characteristics. These outcomes resemble those seen following manipulations of gonadal hormones and are thought to occur because stress influences these hormones during critical periods of development. Research on prenatal stress and human sexual differentiation has produced inconsistent results, perhaps because studies have used small samples and assessed prenatal stress retrospectively. We related maternal self-reports of prenatal stress to childhood gender role behavior in a prospective, population study of 13,998 pregnancies resulting in 14,138 offspring. Neither stress reported during the first 18 weeks of pregnancy nor stress reported from week 19 of pregnancy to week 8 postnatal related to gender role behavior in male offspring at the age of 42 months. In female offspring, maternal reports of stress during both periods showed only small correlations with masculine-typical behavior. Although this relationship remained significant when other factors that related to stress were controlled, these other factors made larger contributions to girls' gender role behavior than did prenatal stress. In addition, in both boys and girls, older male or female siblings, parental adherence to traditional sex roles, maternal use of tobacco or alcohol during pregnancy, and maternal education all related significantly to gender role behavior. Our results suggest that prenatal stress does not influence the development of gender role behavior in boys and appears to have relatively little, if any, influence on gender role behavior in girls.

Child Behavior↗
PubMed2000

The role of brothers and sisters in the gender development of preschool children.

The study examined whether the sex of older siblings influences the gender role development of younger brothers and sisters of age 3 years. Data on the Pre-School Activities Inventory, a measure of gender role behavior that discriminates within as well as between the sexes, were obtained in a general population study for 527 girls and 582 boys with an older sister, 500 girls and 561 boys with an older brother, and 1665 singleton girls and 1707 singleton boys. It was found that boys with older brothers and girls with older sisters were more sex-typed than same-sex singletons who, in turn, were more sex-typed than children with other-sex siblings. Having an older brother was associated with more masculine and less feminine behavior in both boys and girls, whereas boys with older sisters were more feminine but not less masculine and girls with older sisters were less masculine but not more feminine.

Birth Order↗
PubMed1993

The semantics of grammatical gender: a cross-cultural study.

Although most present-day scholars claim that grammatical gender has no meaning correlates, anecdotal evidence dating back to the Greeks suggests that grammatical gender carries connotative meanings of femininity and masculinity. In the present study native German speakers (tested in Germany) and native Spanish speakers (tested in Mexico) judged 54 high-frequency translation equivalents on semantic differential scales chosen to reflect dimensions of evaluation, potency, and activity. Half the words were of feminine gender in German but of masculine gender in Spanish (Type I words), and half were of masculine gender in German and of feminine gender in Spanish (Type II words). As predicted, German speakers judged Type II words higher in potency than Type I words, whereas Spanish speakers judged Type I words higher in potency than Type II words. The conclusion was that grammatical gender does affect meaning.

Adult↗
PubMed1982

Sex role endorsement among homosexual men across the life span.

This study assessed the sex role endorsement of homosexual men at different ages across the life span. A sample of homosexual men from dignity chapters in the northeastern, midwestern, southern, southwestern, and western United States was mailed a demographic questionnaire and th Bem Sex Role Inventory. Respondents were classified into four age brackets and categorized as androgynous, masculine, feminine, and undifferentiated. A pattern of diverse sex role endorsement was found from adolescence to maturity in which gay men were equally androgynous, masculine, feminine, and undifferentiated at each age level. This finding contradicted an earlier study of heterosexual men that reported increasing numbers of androgynous males with age. The contrast suggests that the sex role endorsement of gay men may be very different from their heterosexual counterparts. It was further suggested tht gay men are capable of meshing masculine and feminine aspects of their personalities early as well as later in life, that gay men do not comprise a homogeneous group, and that the stereotype of cross-gender role endorsement is unfounded.

Age Factors↗