Changes in genetic risk for emotional eating across the menstrual cycle: a longitudinal study.

BACKGROUND: Previous studies have shown significant within-person changes in binge eating and emotional eating across the menstrual cycle, with substantial increases in both phenotypes during post-ovulation. Increases in both estradiol and progesterone levels appear to account for these changes in phenotypic risk, possibly via increases in genetic effects. However, to date, no study has examined changes in genetic risk for binge phenotypes (or any other phenotype) across the menstrual cycle. The goal of the present study was to examine within-person changes in genetic risk for emotional eating scores across the menstrual cycle. METHOD: Participants were 230 female twin pairs (460 twins) from the Michigan State University Twin Registry who completed daily measures of emotional eating for 45 consecutive days. Menstrual cycle phase was coded based on dates of menstrual bleeding and daily ovarian hormone levels. RESULTS: Findings revealed important shifts in genetic and environmental influences, where estimates of genetic influences were two times higher in post- as compared with pre-ovulation. Surprisingly, pre-ovulation was marked by a predominance of environmental influences, including shared environmental effects which have not been previously detected for binge eating phenotypes in adulthood. CONCLUSIONS: Our study was the first to examine within-person shifts in genetic and environmental influences on a behavioral phenotype across the menstrual cycle. Results highlight a potentially critical role for these shifts in risk for emotional eating across the menstrual cycle and underscore the need for additional, large-scale studies to identify the genetic and environmental factors contributing to menstrual cycle effects.

The effects of circulating testosterone and pubertal maturation on risk for disordered eating symptoms in adolescent males.

BACKGROUND: Testosterone may be a biological factor that protects males against eating disorders. Elevated prenatal testosterone exposure is linked to lower levels of disordered eating symptoms, but effects emerge only after mid-puberty. Whether circulating levels of testosterone account for decreased risk for disordered eating in boys after mid-puberty is currently unknown; however, animal data support this possibility. In rodents, prenatal testosterone's masculinizing effects on sex-differentiated behaviors emerge during puberty when circulating levels of testosterone increase and 'activate' the expression of masculinized phenotypes. This study investigated whether higher levels of circulating testosterone predict lower levels of disordered eating symptoms in adolescent boys, and in particular whether effects are associated with advancing pubertal maturation. METHOD: Participants were 213 male twins from the Michigan State University Twin Registry. The Minnesota Eating Behavior Survey and Eating Disorder Examination Questionnaire assessed several disordered eating symptoms. The Pubertal Development Scale assessed pubertal status. Afternoon saliva samples were assayed for testosterone using enzyme immunoassays. RESULTS: Consistent with animal data, higher levels of circulating testosterone predicted lower levels of disordered eating symptoms in adolescent boys and effects emerged with advancing puberty. Results were not accounted for by several important covariates, including age, adiposity, or mood/anxiety symptoms. CONCLUSIONS: Findings suggest that elevated circulating testosterone may be protective and underlie decreased risk for eating pathology in males during/after puberty, whereas lower levels of testosterone may increase risk and explain why some, albeit relatively few, males develop eating disorders.

The effects of puberty on genetic risk for disordered eating: evidence for a sex difference.

BACKGROUND: Differences in genetic influences on disordered eating are present across puberty in girls. Heritability is 0% before puberty, but over 50% during and after puberty. Emerging data suggest that these developmental differences may be due to pubertal increases in ovarian hormones. However, a critical piece of evidence is lacking, namely, knowledge of genetic influences on disordered eating across puberty in boys. Boys do not experience increases in ovarian hormones during puberty. Thus, if pubertal increases in genetic effects are present in boys, then factors in addition to ovarian hormones may drive increases in heritability in girls. The current study was the first to examine this possibility in a sample of 1006 male and female twins from the Michigan State University Twin Registry. METHOD: Disordered eating was assessed with the Minnesota Eating Behavior Survey. Pubertal development was assessed with the Pubertal Development Scale. RESULTS: No significant differences in genetic influences on disordered eating were observed in males across any developmental stage. Heritability was 51% in boys during pre-puberty, puberty and young adulthood. By contrast, in girls, genetic factors accounted for 0% of the variance in pre-puberty, but 51% of the variance during puberty and beyond. Sex differences in genetic effects were only significant during pre-puberty, as the best-fitting models constrained heritability to be equal across all males, pubertal females and young adult females. CONCLUSIONS: The results highlight sex-specific effects of puberty on genetic risk for disordered eating and provide indirect evidence of a role for ovarian hormones and/or other female-specific factors.

Dihydrotestosterone activates sexual behavior in adult male hamsters but not in juveniles.

The effect of an androgenic metabolite of testosterone, dihydrotestosterone (DHT), on reproductive behavior and brain androgen receptor (AR) immunoreactivity was compared in juvenile and adult male Syrian hamsters. Prepubertal and adult animals were castrated and treated with 0, 500, or 1000 microg of DHT daily for 1 week and then tested for their ability to engage in mating behavior. The 1000-microg dose of DHT activated intromissions in adult but not prepubertal males. Brains were collected immediately after the behavioral test to investigate whether the lack of a behavioral response to DHT prior to puberty is associated with fewer AR-immunoreactive (AR-ir) cells in the forebrain nuclei that mediate male sexual behavior. In four of the five nuclei within the behavioral circuit that were examined, the number of AR-containing cells was similar in prepubertal and adult males treated with 1000 microg of DHT. Only in the anterior medial amygdala (MeA) was there a greater number of AR-ir cells in adults. These data indicate that (1) DHT does not activate components of male reproductive behavior prior to puberty and (2) the lack of behavioral responsiveness to DHT in prepubertal males is most likely not related to an overall reduction in ARs within the forebrain circuit that mediates mating behavior.

In vivo gonadotropin-releasing hormone secretion in female rats during peripubertal development and on proestrus.

Pubertal development in female rats is characterized by increased LH levels and the appearance of estrogen-dependent afternoon LH mini-surges. In these studies we performed the first analysis of GnRH patterns in peripubertal rats to determine whether there are similar changes in pulsatile GnRH release. Microdialysis samples were collected at 5-min intervals throughout a 5-h afternoon period from 22 rats sampled on a single day between 30-47 days of age. Adult female rats were sampled on proestrus for comparison. In 30- to 33-day-old rats, GnRH release was infrequent (2.7 pulses/5 h; n = 3), whereas intermediate pulse frequencies were observed in 34- to 37-day-old rats (6.4 pulses/5 h; n = 9) and 38- to 42-day-old (5.0 pulses/5 h; n = 5) rats. The highest GnRH pulse frequencies were observed in 43- to 47-day-old rats (9.4 pulses/5 h; n = 5). Mean GnRH pulse amplitude did not vary significantly with age. Animals sampled before vaginal opening (VO) exhibited significantly slower GnRH pulse frequencies than those sampled after vaginal opening (1.3 pulses/5 h pre-VO vs. 7.6 pulses/5 h post-VO; P = 0.01). An afternoon increase in GnRH secretion, defined operationally as a greater than 25% increase in mean GnRH levels in the last half of the sampling period and tentatively termed a mini-surge, was observed in 0%, 33%, 40%, and 60% of 30- to 33-, 34- to 37-, 38- to 42-, and 43- to 47-day-old rats, respectively. An overall increase in GnRH pulse frequency was observed in females displaying a mini-surge (9.0 pulses/5 h with mini-surge compared with 4.7 pulses/5 h with no mini-surge). The mini-surge itself, however, was associated with a late afternoon increase in GnRH pulse amplitude and not in pulse frequency. In adult proestrous rats, peak levels during the GnRH surge were an order of magnitude greater than those reached in pubertal animals. Our findings demonstrate that pubertal maturation in the female rat is associated with an acceleration of GnRH pulse generator activity and that later stages of pubertal maturation are characterized by the appearance of afternoon increases in GnRH release that may underlie previously reported mini-surges in LH.

Pubertal and seasonal plasticity in the amygdala.

The present experiments investigated the effects of pubertal maturation and photoperiod on the size of brain regions that mediate mating behavior in the male Syrian hamster. We hypothesized that the low levels of reproductive behavior exhibited by prepubertal and photoinhibited males would be correlated with morphological changes in the neural circuit that mediates mating behavior. We found that the Nissl-stained cross-sectional area of the posterodorsal subdivision of the medial amygdala was significantly smaller in prepubertal and photoinhibited males compared to photostimulated adult males. These differences appear to be caused by a decrease in somal size of individual cells in the ventral aspect of this nucleus. We also found that prepubertal males have a larger anterior subdivision of the medial amygdala (MeA) compared to adults. This difference in the MeA does not appear to be caused by alteration in somal size since somal size did not differ significantly between juveniles and adults. It is concluded that the neural circuit that mediates male mating behavior in this species is capable of significant morphological plasticity during both pubertal development and in adulthood. Furthermore, these alterations may reflect underlying mechanisms of the deficits in sexual behavior exhibited by prepubertal and photoinhibited males.

Sexual and reproductive behaviors.

The procedures described in this unit include testing procedures for male and female reproductive behaviors, gonadectomy, and hormonal treatments appropriate for inducing male and female reproductive behaviors. Because reproductive behaviors are social behaviors, and therefore require the presence of stimulus animals, the protocols in this unit also provide information on the preparation of stimulus animals. The protocols are written for use with laboratory rats, although a discussion of issues related to species differences in the study of reproductive behaviors is included.

Effects of gonadal steroids during pubertal development on androgen and estrogen receptor-alpha immunoreactivity in the hypothalamus and amygdala.

Perinatal development is often viewed as the major window of time for organization of steroid-sensitive neural circuits by steroid hormones. Behavioral and neuroendocrine responses to steroids are dramatically different before and after puberty, suggesting that puberty is another window of time during which gonadal steroids affect neural development. In the present study, we investigated whether the presence of gonadal hormones during pubertal development affects the number of androgen receptor and estrogen receptor alpha-immunoreactive (AR-ir and ER alpha-ir, respectively) cells in limbic regions. Male Syrian hamsters were castrated either before or after pubertal development, and 4 weeks later they received a single injection of testosterone or oil vehicle 4 h prior to tissue collection. Immunocytochemistry for AR and ER alpha was performed on brain sections from testosterone-treated and oil-treated males, respectively. Adult males that had been castrated before puberty had a greater number of AR-ir cells in the medial preoptic nucleus than adult males that had been castrated after puberty. There were no significant differences in ER alpha-ir cell number in any of the brain regions examined. The demonstration that exposure to gonadal hormones during pubertal development is associated with reduced AR-ir in the medial preoptic nucleus indicates that puberty is a period of neural development during which hormones shape steroid-sensitive neural circuits.

A morning surge in plasma luteinizing hormone coincides with elevated Fos expression in gonadotropin-releasing hormone-immunoreactive neurons in the diurnal rodent, Arvicanthis niloticus.

Arvicanthis niloticus is a diurnal murid rodent from sub-Saharan Africa. Here we report on processes associated with mating in this species in an attempt to elucidate how the neural mechanisms governing temporal organization differ in nocturnal and diurnal species. First, we systematically mapped the distribution of GnRH neurons in adult females. Second, we tested the hypothesis that Arvicanthis differ from nocturnal murid rodents with respect to the timing of the LH surge and the associated increase in Fos expression in GnRH-immunoreactive (IR) neurons. We examined these events around a postpartum estrus. When parturition occurred between zeitgeber time (ZT) 2 and 17 (lights on at ZT 0 and off at ZT 12; there are 24 ZT units a day, each equivalent to 1 standard hour), we collected blood and perfused females at ZT 17, 20, 23, or 2. A sharp peak in plasma LH occurred at ZT 20, and a 10-fold increase in the percentage of GnRH-IR neurons that expressed Fos-IR occurred between ZT 17 and 20. By contrast, this rise occurs in nocturnal rodents during the last few hours of the light period. This is the first indication of a difference between nocturnal and diurnal animals with respect to neural mechanisms associated with a precisely timed event of known significance.

GnRH mRNA increases with puberty in the male Syrian hamster brain.

Puberty in the male Syrian hamster (Mesocricetus auratus) is characterized by decreased responsiveness to testosterone mediated negative feedback, but the neural mechanism for this change remains elusive. We hypothesized that decreased inhibition of the gonadotropin-releasing hormone (GnRH) system results in increased neurosecretory activity, which includes an increase in GnRH gene expression. This study examined GnRH mRNA in male hamsters before and after puberty, and sought to determine if any increase in mRNA was specific to particular subpopulations of GnRH neurones. Brains were collected from 21-day-old prepubertal males (n = 5) and 56-day-old postpubertal males (n = 5). Alternate 10 microm coronal sections from fresh-frozen brains were collected throughout the septo-hypothalamic region, and 25% of those sections were processed for in-situ hybridization histochemistry using an 35S-riboprobe complementary to hamster GnRH. No differences were observed in the number of GnRH mRNA expressing cells in any region, but in the diagonal band of Broca (DBB)/organum vasculosum of the lamina terminalis (OVLT) there was a significant increase in labelling intensity (defined as area of the cell occupied by silver grains) in postpubertal males. A second analysis compared the frequency distributions of cells based on labelling intensity between prepubertal and postpubertal males. This analysis revealed significant differences between the two frequency distributions in all areas analysed (DBB/OVLT, medial septum (MS), and preoptic area (POA)). Furthermore, examining the distribution of cells in these regions revealed a shift to the right in the postpubertal population of cells, which indicated an increased number of GnRH neurones with greater labelling intensity. These data clearly demonstrate increased GnRH mRNA during puberty. Furthermore, they suggest that the previous observation of brain region specific pubertal decreases in GnRH-immunoreactivity only within the DBB/OVLT and MS but not the POA are not due to differential levels of GnRH gene expression, but could indicate increased release from these neurones during puberty.