Otoacoustic emissions,auditory evoked potentials and self-reported gender in people affected by disorders of sex development (DSD)

Both otoacoustic emissions (OAEs) and auditory evoked potentials (AEPs) are sexually dimorphic, and both are believed to be influenced by prenatal androgen exposure. OAEs and AEPs were collected from people affected by 1 of 3 categories of disorders of sex development (DSD) — (1) women with complete androgen insensitivity syndrome (CAIS); (2) women with congenital adrenal hyperplasia (CAH); and (3) individuals with 46,XY DSD including prenatal androgen exposure who developed a male gender despite initial rearing as females (men with DSD). Gender identity (GI) and role (GR) were measured both retrospectively and at the time of study participation, using standardized questionnaires. The main objective of this study was to determine if patterns of OAEs and AEPs correlate with gender in people affected by DSD and in controls. A second objective was to assess if OAE and AEP patterns differed according to degrees of prenatal androgen exposure across groups. Control males, men with DSD, and women with CAH produced fewer spontaneous OAEs (SOAEs) – the male-typical pattern – than control females and women with CAIS. Additionally, the number of SOAEs produced correlated with gender development across all groups tested. Although some sex differences in AEPs were observed between control males and females, AEP measures did not correlate with gender development, nor did they vary according to degrees of prenatal androgen exposure, among people with DSD. Thus, OAEs, but not AEPs, may prove useful as bioassays for assessing early brain exposure to androgens and predicting gender development in people with DSD.     

Prenatal androgen exposure and children's aggressive behavior and activity level

Some human behaviors, including aggression and activity level, differ on average for males and females. Here we report findings from two studies investigating possible relations between prenatal androgen and children's aggression and activity level. For study 1, aggression and activity level scores for 43 girls and 38 boys, aged 4 to 11 years, with congenital adrenal hyperplasia (CAH, a genetic condition causing increased adrenal androgen production beginning prenatally) were compared to those of similarly-aged, unaffected relatives (41 girls, 31 boys). Girls with CAH scored higher on aggression than unaffected girls, d = 0.69, and unaffected boys scored higher on activity level than unaffected girls, d = 0.50. No other group differences were significant. For study 2, the relationship of amniotic fluid testosterone to aggression and activity level was investigated in typically-developing children (48 girls, 44 boys), aged 3 to 5 years. Boys scored higher than girls on aggression, d = 0.41, and activity level, d = 0.50. However, amniotic fluid testosterone was not a significant predictor of aggression or activity level for either sex. The results of the two studies provide some support for an influence of prenatal androgen exposure on children's aggressive behavior, but not activity level. The within-sex variation in amniotic fluid testosterone may not be sufficient to allow reliable assessment of relations to aggression or activity level.     

Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys

The masculinizing effects of prenatal androgens on human neurobehavioral development are well established. Also, the early postnatal surge of androgens in male infants, or mini-puberty, has been well documented and is known to influence physiological development, including penile growth. However, neurobehavioral effects of androgen exposure during mini-puberty are largely unknown. The main aim of the current study was to evaluate possible neurobehavioral consequences of mini-puberty by relating penile growth in the early postnatal period to subsequent behavior. Using multiple linear regression, we demonstrated that penile growth between birth and three months postnatal, concurrent with mini-puberty, significantly predicted increased masculine/decreased feminine behavior assessed using the Pre-school Activities Inventory (PSAI) in 81 healthy boys at 3 to 4 years of age. When we controlled for other potential influences on masculine/feminine behavior and/or penile growth, including variance in androgen exposure prenatally and body growth postnally, the predictive value of penile growth in the early postnatal period persisted. More specifically, prenatal androgen exposure, reflected in the measurement of anogenital distance (AGD), and early postnatal androgen exposure, reflected in penile growth from birth to 3 months, were significant predictors of increased masculine/decreased feminine behavior, with each accounting for unique variance. Our findings suggest that independent associations of PSAI with AGD at birth and with penile growth during mini-puberty reflect prenatal and early postnatal androgen exposures respectively. Thus, we provide a novel and readily available approach for assessing effects of early androgen exposures, as well as novel evidence that early postnatal aes human neurobehavioral development.     

Effects of gender and age on median and ulnar nerve sensory responses over ring finger

ObjectiveTo analyze the effect of gender on median nerve (MN) and ulnar nerve (UN) sensorial responses over ring finger (RF).Materials and methodsResults of individuals admitted to our ENMG laboratory between June 2011 and March 2012 for nerve conduction studies (NCSs) were retrospectively analyzed. Sensory NCSs were performed by standard antidromic technique.ResultsTotally, 112 normal recordings belong to 100 patients were included. Mean antidromic sensory conduction velocity of MNs (wrist-to-second finger) or UNs (wrist-to-fifth finger) was not different between two genders. Mean sensory nerve action potential (SNAP) amplitude of MN from second finger was also not different between two genders. However, mean SNAP amplitude of UN from fifth finger was higher in females. In RF’s sensorial response studies; mean peak latency of MN was similar between females and males (3.05 ± 0.25 ms vs. 3.14 ± 0.29 ms, p = 0.111), whereas one of UN was shorter in females (2.86 ± 0.22 ms vs. 3.04 ± 0.31 ms, p = 0.001). MN to UN latency difference to RF was greater in females than males (0.19 ± 0.15 ms vs. 0.10 ± 0.16 ms, p = 0.007). Mean SNAP amplitude of MN and UN were both higher in females than males (17.9 ± 7.1 μV vs. 14.1 ± 5.5 μV, p = 0.011 and 18.5 ± 8.0 μV vs. 12.9 ± 6.1 μV, p = 0.0009, respectively). All data of NCSs were re-analyzed after adjustment for age, and obtained findings regarding effect of aging are also included.ConclusionGender has a prominent effect on RF’s sensorial responses. Normative values regarding them should be prepared with adjustment for gender.     

No effects of androgen receptor gene CAG and GGC repeat polymorphisms on digit ratio (2D:4D): a comprehensive meta-analysis and critical evaluation of research

A series of meta-analyses assessed whether differentially efficacious variants (CAG and GGC repeat-length polymorphisms) of the human androgen receptor gene are associated with digit ratio (2D:4D), a widely investigated putative pointer to prenatal androgen action. Extensive literature search strategies identified a maximum of 18 samples (total N = 2909) vs. 5 samples (N = 1497) for the CAG-related vs. GGC-related meta-analyses, respectively. In contrast to a small-sample (N = 50) initial report, widely cited affirmatively in the literature, meta-analysis of the entire retrievable evidence base did not support any associations between CAG variants and right-hand, left-hand, or right-minus-left-hand 2D:4D. Effects of GGC variants on digit ratios likewise were almost exactly null. For the CAG literature, time trend analysis indicated shrinking effects among more recent studies. Both quantitative and qualitative citation analyses documented that citation bias exists in the research literature: CAG-related studies yielding larger effects were cited more frequently within the same time unit, and the initial, unreplicated report continued to be cited frequently and mostly solely as well as confirmatively, while non-replications were cited much less often. The meta-analytical null findings, along with several further strands of evidence consistent with these, undermine one validity claim for 2D:4D as a retrospective pointer to prenatal testosterone action. Discussed are alternative interpretations of the evidence and avenues for future research.     

Influence of age,gender, educational level and self-estimation of skin type on sun exposure habits and readiness to increase sun protection

Background: Sun exposure habits and the propensity to undertake sun protection differ between individuals. Not least in primary prevention of skin cancer, aiming at reducing ultraviolet (UV) exposure, knowledge about these factors may be of importance. The aim of the present study was to investigate, in a primary health care (PHC) population, the relationship between sun exposure habits/sun protection behaviour/readiness to increase sun protection and gender, age, educational level and skin UV-sensitivity. Methods: The baseline data from a previously performed RCT on skin cancer prevention was used. 415 patients, aged >18 years, visiting a PHC centre in southern Sweden, filled-out a questionnaire mapping sun exposure, readiness to increase sun protection according to the Transtheoretical Model of Behaviour Change (TTM), and the above mentioned factors. Results: Female gender was associated with more frequent suntanning (p < 0.001) and sunbed use (p < 0.05), but also with more extensive sunscreen use (p < 0.001). High age was in general associated with low level of sun exposure and high level of protection. Subjects with low educational level reported less frequent sunscreen use than those with higher educational level, and also chose lower SPF (p < 0.001). For almost all parameters, high skin UV-sensitivity was associated with markedly lower sun exposure (p < 0.001) and more pronounced readiness to increase sun protection. Females and subjects with high educational level reported higher readiness to increase sunscreen use than males and subjects with lower educational level (p < 0.001). Conclusions: Gender, age, educational level and skin type appear to be important factors affecting sun exposure habits and sun protection behaviour, which supports the idea of appropriate mapping of these factors in patients in order to individualise sun protection advice according to the individual patient situation and capabilities.     

Effect of artificial vs. natural rearing on milk yield,kid growth and cost in Payoya autochthonous dairy goats

Seventy full lactations of Payoya dairy goats were used to study the effect of two different kid-rearing systems, natural or artificial, on milk yield, composition, hygiene-sanitary quality, kid growth and rearing cost. Two animal groups were established, one with goats under natural rearing (NS) and the other under artificial rearing (AR). In the NS group, the kids had free access to goat milk 18–20 h a day and were suckled up to 5 weeks of age and then the dams were milked twice daily. Dams in the AR were separated from their kids at 48 h post-partum; then, kids were reared artificially, and the dams were milked twice daily. The number of animals used in each type of rearing system was 35 (23 goats giving birth to twins and 12 goats giving birth to a single kid). Each week during suckling phase the volume of milk produced was measured, and individual samples were taken. From 5th week and until 210 days lactation, test-day yields recorded at intervals of 30 ± 3 days were obtained. The chemical composition of the milk, the bacteriology, and the somatic cell count was analyzed. The kids of both sexes were assigned to two groups, natural suckling (NS, n = 58) and ad libitum artificial rearing (AR, n = 58). Within each treatment, two groups of kids were formed depending on prolificacy: first group with kids from single birth (n = 12) and the second with twin kids (n = 46). Birth weight and weight every week upto the 4th week of life were recorded. During the 5 weeks of lactation the total milk yield per goat was higher for the NS group (140.2 L vs. 95.4 L; P < 0.001), although the total amount of marketable milk was greater for the AR group, with a difference of some 21 L (P < 0.05). Throughout the entire lactation the milk yield was higher in the group of natural rearing (total yield of 508 L vs. 400 L; P < 0.05). Although a significant effect of prolificacy was found during suckling phase (P < 0.001), during 30 weeks of lactation this factor did not affect milk yield (P > 0.05). For the milk composition and hygiene-sanitary quality there were no effects on the type of rearing system or the type of birth (P > 0.05). No significant effect was observed either for the feeding system or the sex or the prolificacy on the live weight of the kids at 28 days and the postnatal growth rate from birth to 28 days (P > 0.05). Natural rearing system had higher cost per kid comparing with artificial rearing system (€18.63/kid vs. €14.70/kid, respectively). However, when comparing total incomes during a full lactation, goats with natural rearing system had a higher income because of increment of total milk production (€29.95/kid).     

Cancer mortality and occupational exposure to aromatic amines and inhalable aerosols in rubber tire manufacturing in Poland

Aim: Most data on carcinogenic risk in the rubber industry are based on data from Western countries. This study assessed cancer risks in a retrospective cohort in a Polish tire manufacturing plant, relying on quantified exposure to inhalable aerosols and aromatic amines instead of job titles or external comparisons. Methods: Cumulative exposure for all exposures was assigned to cohort members based on estimates from a company-specific JEM. Cancer risks associated with cumulative exposure adjusted for co-exposures, gender and year of birth were calculated. Results: Exposure levels were higher for women than for men. Aromatic amine exposure was significantly associated with increased urinary bladder cancer risk (RR = 7.32–8.27), depending on exposure level, and prostate cancer at low levels only (RR = 5.86). In women, increased risks were found for all cancers (RR = 2.50) and of the digestive organs and peritoneum (RR = 4.54) at low level only, while an exposure-response association with breast cancer risk was found. Inhalable aerosol exposure was associated with cancers of the liver and intrahepatic bile ducts in a dose-dependent manner, while dose-dependent reduced risks were found for respiratory cancers (most notably the larynx) and cancer of the colon. Conclusions: Increased risks for specific cancer sites in this rubber plant were similar to Western Europe and the US. However, several cancer risks were gender-specific which could relate to higher exposure levels in women or to differences in exposures to chemicals not assessed in this study.     

Body mass index,height and early-onset basal cell carcinoma in a case-control study

IntroductionBasal cell carcinoma (BCC) is the most common malignancy in the US. Body mass index (BMI) and height have been associated with a variety of cancer types, yet the evidence regarding BCC is limited. Therefore, we evaluated BMI and height in relation to early-onset BCC (under age 40) and explored the potential role of ultraviolet (UV) radiation exposure and estrogen-related exposures in the BMI-BCC relationship.MethodsBCC cases (n = 377) were identified through a central dermatopathology facility in Connecticut. Control subjects (n = 389) with benign skin conditions were randomly sampled from the same database and frequency matched to cases on age (median = 36, interquartile range 33–39), gender, and biopsy site. Participants reported weight (usual adult and at age 18), adult height, sociodemographic, phenotypic, and medical characteristics, and prior UV exposures. We calculated multivariate odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models.ResultsAdult BMI was inversely associated with early-onset BCC (obese vs. normal OR = 0.43, 95% CI = 0.26–0.71). A similar inverse association was present for BMI at age 18 (OR = 0.54, 95% CI = 0.34–0.85). Excluding UV exposures from the BMI models and including estrogen-related exposures among women only did not alter the association between BMI and BCC, indicating limited mediation or confounding. We did not observe an association between adult height and BCC (OR per cm = 1.00, 95% CI = 0.98–1.02).ConclusionsWe found a significant inverse association between BMI and early-onset BCC, but no association between height and BCC. This association was not explained by UV exposures or estrogen-related exposures in women.     

The biology of human psychosexual differentiation

Most attempts to identify biological underpinnings of gender identity and sexual orientation in humans have investigated effects of sex steroids, so pivotal in the differentiation of the genitalia, showing strong parallels between animals and the human. The information on humans is derived from the so-called 'experiments of nature', clinical entities with a lesser-than-normal androgen exposure in XY subjects and a higher than normal androgen exposure in XX subjects. Prenatal androgenization appears to predispose to a male gender identity development, but apparently not decisively since 40-50% of 46,XY intersexed children with a history of prenatal androgen exposure do not develop a male gender identity. Obviously, male-to-female transsexuals, with a normal androgen exposure prenatally (there is no serious evidence to the contrary) develop a female gender identity, through unknown biological mechanisms apparently overriding the effects of prenatal androgens. The latest studies in 46, XX subjects exposed to prenatal androgens show that prenatal androgenization of 46,XX fetuses leads to marked masculinization of later gender-related behavior but does not lead to gender confusion/dysphoria. The example of female-to-male transsexuals, without evidence of prenatal androgen exposure, indicates that a male gender identity can develop without a significant androgen stimulus. So we are far away from any comprehensive understanding of hormonal imprinting on gender identity formation. Brain studies in homosexuals have not held up in replication studies or are in need of replication in transsexuals. Genetic studies and the fraternal birth order hypothesis provide indications of familial clustering of homosexuality but in many homosexuals these genetic patterns cannot be identified. The biological explanations advanced for the birth order hypothesis lack any experimental support.     

The effect of age and gender on 38 chemical element contents in human iliac crest investigated by instrumental neutron activation analysis

ProjectTo understand the role of major, minor, and trace elements in the etiology of bone diseases including osteoporosis, it is necessary to determine the normal levels and age-related changes of bone chemical elements.ProcedureThe effect of age and gender on 38 chemical element contents in intact iliac crest of 84 apparently healthy 15–55 years old women (n=38) and men (n=46) was investigated by neutron activation analysis.ResultsMean values (M±SEM) for mass fraction (on dry weight basis) of Ca, Cl, Co, Fe, K, Mg, Mn, Na, P, Rb, Sr, and Zn for both female and male taken together were Ca – 169±3 g/kg, Cl – 1490±43 mg/kg, Co – 0.0073±0.0024 mg/kg, Fe – 177±24 mg/kg, K – 1820±79 mg/kg, Mg – 1840±48 mg/kg, Mn – 0.316±0.013 mg/kg, Na – 4970±87 mg/kg, P – 79.7±1.5 g/kg, Rb – 1.89±0.22 mg/kg, Sr – 312±15 mg/kg, and Zn – 65.9±3.4 mg/kg, respectively. The upper limit of mean contents of Cs, Eu, Hg, Sb, Sc, and Se were Cs≤0.09 mg/kg, Eu≤0.005 mg/kg, Hg≤0.005 mg/kg, Sb≤0.004 mg/kg, Sc≤0.001 mg/kg, and Se≤0.1 mg/kg, respectively. In all bone samples the contents of Ag, As, Au, Ba, Br, Cd, Ce, Cr, Gd, Hf, La, Lu, Nd, Sm, Ta, Tb, Th, U, Yb, and Zr were under detection limits.ConclusionsThe Ca, Mg, and P contents decrease with age, regardless of gender. Higher Ca, Mg, P, and Sr mass fractions as well as lower Fe content are typical of female iliac crest as compared to those in male bone.     

Long-term effects of oxandrolone treatment in childhood on neurocognition,quality of life and social–emotional functioning in young adults with Turner syndrome

Turner syndrome (TS) is the result of (partial) absence of one X-chromosome. Besides short stature, gonadal dysgenesis and other physical aspects, TS women have typical psychological features. Since psychological effects of androgen exposure in childhood probably are long-lasting, we explored long-term psychological functioning after oxandrolone (Ox) therapy during childhood in adults with TS in terms of neurocognition, quality of life and social–emotional functioning. During the initial study, girls were treated with growth hormone (GH) combined with placebo (Pl), Ox 0.03 mg/kg/day, or Ox 0.06 mg/kg/day from the age of eight, and estrogen from the age of twelve. Sixty-eight women participated in the current double-blinded follow-up study (mean age 24.0 years, mean time since stopping GH/Ox 8.7 years). We found no effects on neurocognition. Concerning quality of life women treated with Ox had higher anxiety levels (STAI 37.4 ± 8.4 vs 31.8 ± 5.0, p = 0.002) and higher scores on the depression subscale of the SCL-90-R (25.7 ± 10.7 vs 20.5 ± 4.7, p = 0.01). Regarding social–emotional functioning, emotion perception for fearful faces was lower in the Ox-treated patients, without effect on interpersonal behavior. Our exploratory study is the first to suggest that androgen treatment in adolescence possibly has long-term effects on adult quality of life and social–emotional functioning. However, differences are small and clinical implications of our results seem limited. Therefore we would not recommend against the use of Ox in light of psychological consequences.     

Examining the association between cigarette smoking and colorectal cancer using historical case–control data

Background: The majority of recent, well-designed studies have shown that long-term cigarette smoking increases colorectal cancer risk, but older studies with shorter durations of exposure often found no association. This study aimed to examine colorectal cancer risk by smoking exposure using data collected in the late-1950s and early-1960s. Methods: This case–control study examined colorectal cancer risk by lifetime smoking history. There were 1365 patients who visited Roswell Park Cancer Institute (RPCI) between 1957 and 1965 diagnosed with primary, incident colorectal cancers that were matched to 4096 malignancy-free controls on gender and age. Odds ratios were calculated using separate logistic regression models for each smoking exposure, while controlling for other tobacco use, county of residence, race, age, gender, and body mass index (BMI). Results: The adjusted OR for individuals who reported their greatest level of smoking to be more than 1 pack/day was 0.87 (95% CI = 0.67–1.15). Among those who smoked 42 or more years, the adjusted OR was 0.89 (95% CI = 0.68–1.15) compared to those who never smoked. For individuals who smoked more than 45 pack-years, the OR was 0.92 (95% CI = 0.72–1.19). The results did not differ significantly by gender, although men had considerably greater exposure compared to women. Results also did not differ by colorectal sub-site. Conclusion: No association was found between long-term cigarette smoking and colorectal cancer risk. These results are in accord with studies that followed cohorts throughout the 1950s and 1960s. Methodological limitations, such as missing data on covariates and the higher incidence of smoking-related illness in a hospital setting, may have contributed to the null results found in this study. Prolonged population exposure to cigarettes and perhaps a changing product may explain why more recent studies have reported a positive association between smoking and colorectal cancer.     

Children and Adolescents with Gender Dysphoria in Israel: Increasing Referral and Fertility Preservation Rates

Objective: To describe patient characteristics at presentation, management, and fertility preservation rates among a cohort of Israeli children and adolescents with gender dysphoria (GD).Methods: We performed a retrospective chart review of 106 consecutive children and adolescents with GD (<18 years) referred to and followed at the multidisciplinary Israeli Pediatric Gender Dysphoria Clinic from March 2013 through December 2018.Results: Of the 106 patients, 10 were prepubertal (9 prepubertal transgender females), and 96 were pubertal (38 pubertal transgender females). The GD population increased 11-fold since the establishment of our clinic in 2013. The subject's median age at referral was 15.5 years (range, 4.6 to 18 years). At the time of referral, 91 (95%) of the pubertal group had completed sexual maturation in their assigned gender at birth. Thirteen (13.5%) patients had attempted suicide, and 11 (11.5%) reported having had suicidal thoughts. Fourteen (45%) pubertal transgender females and 3 (6.5%) pubertal transgender males completed fertility preservation. Gonadotropin-releasing hormone analog treatment was prescribed in 77 (80%) patients at a mean age of 15.9 ± 1.6 years. Gender-affirming hormones were prescribed in 61 (64%) patients at a mean age of 16.5 ± 1.3 years. No severe side effects were recorded. Two (2%) of the pubertal group expressed regret about medical treatment.Conclusion: Children and adolescents with GD are presenting for medical attention at increasing rates. Israeli adolescents with GD have high fertility preservation rates, perhaps attributable to cultural perspectives. Taking advantage of the option to preserve fertility can be achieved when proper counseling is both available and promoted by medical personnel.Abbreviations: GAH = gender-affirming hormone; GD = gender dysphoria; GnRHa = gonadotropin-releasing hormone analog; MHP = mental health professional     

Developmental fluoxetine exposure increases behavioral despair and alters epigenetic regulation of the hippocampal BDNF gene in adult female offspring

A growing number of infants are exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. Perinatal exposure to SSRI medications alter neuroplasticity and increase depressive- and anxiety-related behaviors, particularly in male offspring as little work has been done in female offspring to date. The long-term effects of SSRI on development can also differ with previous exposure to prenatal stress, a model of maternal depression. Because of the limited work done on the role of developmental SSRI exposure on neurobehavioral outcomes in female offspring, the aim of the present study was to investigate how developmental fluoxetine exposure affects anxiety and depression-like behavior, as well as the regulation of hippocampal brain-derived neurotrophic factor (BDNF) signaling in the hippocampus of adult female offspring. To do this female Sprague–Dawley rat offspring were exposed to prenatal stress and fluoxetine via the dam, for a total of four groups of female offspring: 1) No Stress + Vehicle, 2) No Stress + Fluoxetine, 3) Prenatal Stress + Vehicle, and 4) Prenatal Stress + Fluoxetine. Primary results show that, in adult female offspring, developmental SSRI exposure significantly increases behavioral despair measures on the forced swim test, decreases hippocampal BDNF exon IV mRNA levels, and increases levels of the repressive histone 3 lysine 27 tri-methylated mark at the corresponding promoter. There was also a significant negative correlation between hippocampal BDNF exon IV mRNA levels and immobility in the forced swim test. No effects of prenatal stress or developmental fluoxetine exposure were seen on tests of anxiety-like behavior. This research provides important evidence for the long-term programming effects of early-life exposure to SSRIs on female offspring, particularily with regard to affect–related behaviors and their underlying molecular mechanisms.     

Effect of essential oils,such as raspberry ketone and its derivatives,on antiandrogenic activity based on in vitro reporter gene assay

The effect of essential oils, such as raspberry ketone, on androgen (AR) receptor was investigated using a MDA-kb2 human breast cancer cell line for predicting potential AR activity. Among them, eugenol had the highest AR antagonistic activity with its IC₅₀ value of 19 μM. Raspberry ketone, which has threefold higher anti-obese activity than that of capsaicin, also had AR antagonist activity with its IC₅₀ value of 252 μM. Based on these findings, a more precise CoMFA model was proposed as follows: pIC₅₀ [log (1/IC₅₀)] = 3.77 + [CoMFA field terms] (n = 39, s = 0.249, r² = 0.834, s_cv = 0.507, q² = 0.311 (three components).     

Non-ovarian aromatization is required to activate female sexual motivation in testosterone-treated ovariectomized quail

Although aromatase is expressed in both male and female brains, its functional significance in females remains poorly understood. In female quail, sexual receptivity is activated by estrogens. However it is not known whether sexual motivation is similarly estrogen-dependent and whether estrogens locally produced in the brain contribute to these behavioral responses. Four main experiments were designed to address these questions. In Experiment 1 chronic treatment of females with the anti-estrogen tamoxifen decreased their receptivity, confirming that this response is under the control of estrogens. In Experiment 2 chronic treatment with tamoxifen significantly decreased sexual motivation as treated females no longer approached a sexual partner. In Experiment 3 (a) ovariectomy (OVX) induced a significant decrease of time spent near the male and a significantly decreased receptivity compared to gonadally intact females, (b) treatment with testosterone (OVX + T) partially restored these responses and (c) this effect of T was prevented when estradiol synthesis was inhibited by the potent aromatase inhibitor Vorozole (OVX + T + VOR). Serum estradiol concentration was significantly higher in OVX + T than in OVX or OVX + T + VOR females. Together these data demonstrate that treatment of OVX females with T increases sexual motivation and that these effects are mediated at least in part by non-gonadal aromatization of the androgen. Finally, assays of aromatase activity on brain and peripheral tissues (Experiment 4) strongly suggest that brain aromatization contributes to behavioral effects observed here following T treatment but alternative sources of estrogens (e.g. liver) should also be considered.     

Effect of resistance exercise on muscle steroid receptor protein content in strength-trained men and women

The purpose of this study was to examine the acute effect of resistance exercise (RE) on muscle androgen receptor (AR) and glucocorticoid receptor (GR) protein content. Fifteen resistance-trained men (n = 8; 21 ± 1 years, 175.3 ± 6.7 cm, 90.8 ± 11.6 kg) and women (n = 7; 24 ± 5 years, 164.6 ± 6.7 cm, 76.4 ± 15.6 kg) completed 6 sets of 10 repetitions of heavy squats. Blood samples were obtained before RE, after 3 and 6 sets of squats, and 5, 15, 30 and 70 min after RE. Muscle biopsies from the vastus lateralis were obtained before RE, and 10 min and 70 min after RE. Blood samples were analyzed for total and free testosterone concentrations and muscle samples were analyzed for AR and GR protein content. Circulating total testosterone increased significantly (p ≤ 0.05) in men and free testosterone increased in men and women with exercise. AR was significantly reduced at 70 min post-exercise in men and at 10 min post-exercise in women compared to pre-exercise. There were no changes in GR following RE, but GR was significantly higher in women compared to men. These findings support a current paradigm for stabilization followed by a reduction and then a rebound in the acute AR response to RE but demonstrate that gender differences exist in the timeline of the AR response.     

Early life undernutrition and adult height: The Dutch famine of 1944–45

Current research shows strong associations between adult height and several positive outcomes such as higher cognitive skills, better earning capacity, increased chance of marriage and better health. It is therefore relevant to investigate the determinants of adult height. There is mixed evidence on the effects of undernutrition during early life on adult height. Therefore, our study aims at assessing the impact of undernutrition during gestation and at ages younger than 15 on adult height.We used data from the Longitudinal Aging Study Amsterdam. Exposure to undernutrition was determined by place of residence during the Dutch famine during World War II. Included respondents were born between 15 May 1930 and 1 November 1945 and lived in the northern part of the Netherlands during the famine period (n = 1008). Exposure data was collected using interviews and questionnaires and adult height was measured. Exposed and non-exposed respondents were classified in the age categories pregnancy- age 1 (n = 85), age 1–5 (n = 323), age 6–10 (n = 326) or puberty (age 11–15, n = 274). Linear regression analyses were used to test the associations of adult height with exposure. The robustness of the regression results was tested with sensitivity analyses.In the models adjusted for covariates (i.e., number of siblings, education level of parents, and year of birth) and stratified by gender, adult height was significantly shorter for females exposed at ages younger than 1 (−4.45 cm [−7.44–−1.47]) or at ages younger than 2 (−4.08 cm [−7.20–−0.94]). The results for males were only borderline significant for exposure under age 1 (−3.16 [−6.82–0.49]) and significant for exposure under age 2 (−4.09 cm [−7.20–−0.96]). Exposure to the Dutch famine at other ages was not consistently significantly associated with adult height.In terms of public health relevance, the study’s results further underpin the importance of supporting pregnant women and young parents exposed to undernutrition.     

A refinement and validation of the Monash Canine Personality Questionnaire (MCPQ)

The investigation of canine personality has failed to find strong agreement between studies as to its structure. The area has been hampered by a reliance on human personality models and by a tendency to limit the types of dogs used as subjects. These problems were recently addressed during the development of the Monash Canine Personality Questionnaire (MCPQ). In this follow-up study, over 450 participants provided demographic information about themselves and their dog and completed the MCPQ for their dog. Structural Equation Modelling results necessitated reassessing the original data and reanalysis suggested a more succinct questionnaire, the MCPQ-R, to measure five dimensions of canine personality very similar to those revealed in earlier work (extraversion, motivation, training focus, amicability and neuroticism). Owner reports of personality were generally consistent across demographic variables for all five canine personality subscales. There was no association between any subscale score and owner gender or education level, or dog sex or sexual status (desexed or not desexed). Significant, but generally weak associations were found for owner age and Extraversion (r = 0.17, P < 0.001), owner knowledge of their dog and Training Focus (r = 0.22, P < 0.001), time spent inside and Extraversion (r = ?0.13, P = 0.007), dog age and Extraversion (r = 0.14, P = 0.004), Training Focus and Extraversion (r = 0.13, P = 0.007), dog height and Neuroticism (r = ?0.20, P < 0.001) and dog height and Amicability (r = 0.2, P < 0.001), dog weight and Neuroticism (r = ?0.17, P < 0.01) and dog weight and Amicability (r = 0.19, P < 0.01). There were also few differences in personality ratings across recognised purebred dog breed groups, although Working Dogs and Terriers scored significantly more highly on the Extraverted subscale than other groups (P < 0.001) and Working Dogs and Gundogs scored more highly on the Training Focus subscale (P < 0.001). These results are consistent with the view that the MCPQ-R assesses a construct, canine personality, which is relatively stable and comprised of five dimensions.