Julia L. Zehr

Pubertal hormones organize the adolescent brain and behavior.

Maturation of the reproductive system during puberty results in elevated levels of gonadal steroid hormones. These hormones sculpt neural circuits during adolescence, a time of dramatic rewiring of the nervous system. Here, we review the evidence that steroid-dependent organization of the adolescent brain programs a variety of adult behaviors in animals and humans. Converging lines of evidence indicate that adolescence may be a sensitive period for steroid-dependent brain organization and that variation in the timing of interactions between the hormones of puberty and the adolescent brain leads to individual differences in adult behavior and risk of sex-biased psychopathologies.

Pubertal hormones modulate the addition of new cells to sexually dimorphic brain regions.

New cells, including neurons, arise in several brain regions during puberty in rats. Sex differences in pubertal addition of cells coincide with adult sexual dimorphisms: for each region, the sex that gains more cells during puberty has a larger volume in adulthood. Removing gonadal hormones before puberty eliminates these sex differences, indicating that gonadal steroids direct the addition of new cells during puberty to maintain and accentuate sexual dimorphisms in the adult brain.

Gonadal hormones masculinize and defeminize reproductive behaviors during puberty in the male Syrian hamster

Three experiments were conducted to test whether testicular hormones secreted during puberty masculinize and defeminize the expression of adult reproductive behavior. Experiment 1 tested the hypothesis that gonadal hormones during puberty masculinize behavioral responses to testosterone (T) in adulthood. Male hamsters were castrated either before puberty (noTduringP) or after puberty (TduringP). All males were implanted with a 2.5-mg T pellet 6 weeks following castration and tested once for masculine reproductive behavior 7 days after the onset of T replacement. TduringP males displayed significantly more mounts, intromissions, and ejaculations than noTduringP males. Experiment 2 tested the hypothesis that gonadal hormones during puberty defeminize behavioral responses to estrogen (EB) and progesterone (P). Eight weeks following castration, noTduringP and TduringP males were primed with EB and P and tested for lordosis behavior with a stud male. Behavioral responses of males were compared to that of ovariectomized (OVX) and hormone primed females. NoTduringP males and OVX females displayed significantly shorter lordosis latencies than TduringP males. Experiment 3 investigated whether prolonged T treatment or sexual experience could reverse the deficits in masculine behavior caused by the absence of T during puberty. Extending the T treatment from 7 to 17 days did not ameliorate the deficits in masculine behavior caused by absence of T during puberty. Similarly, when the level of sexual experience was increased from one to three tests, the deficits in masculine behavior persisted. These studies demonstrate that gonadal hormones during puberty further masculinize and defeminize neural circuits and behavioral responsiveness to steroid hormones in adulthood.

Maternal responsiveness increases during pregnancy and after estrogen treatment in macaques

Maternal responsiveness in primates has long been considered emancipated from endocrine factors and entirely dependent on experience and cognition. Here we report that group-living pigtail macaque females increased their rate of interaction with infants in the last weeks of pregnancy in correspondence with an increase in plasma levels of estradiol and progesterone. Estrogen treatment increased the rate at which ovariectomized rhesus females interacted with infants. This is the first evidence that steroid hormones influence maternal responsiveness in anthropoid primates. All untreated ovariectomized females and nonpregnant females interacted with infants, indicating that although estrogen can enhance responsiveness to infants, ovarian or pregnancy hormones are not necessary for the expression of infant-directed behavior in female macaques. The findings of this study suggest fundamental similarities, rather than differences, in the endocrine modulation of maternal responsiveness in primates and other mammals.

Puberty: A Finishing School for Male Social Behavior

Abstract: The classical view of steroid‐dependent organization of brain and behavior holds that gonadal steroid hormones, acting during an early critical period of development, cause permanent structural changes in neural circuits that determine behavioral responses to hormones in adulthood. This classical view has been modified to incorporate evidence that organizational effects of steroids can occur outside of the established perinatal critical period and that multiple critical periods may exist during development. Experiments in this laboratory indicate that steroid‐dependent organization of neural circuits underlying male social behaviors occurs during puberty. This work shows that adult‐typical reproductive and flank marking behaviors cannot be activated by gonadal steroids in male Syrian hamsters prior to puberty, suggesting that developmentally timed processes during puberty render the nervous system responsive to activating effects of gonadal steroids in adulthood. Additional experiments demonstrate that the presence or absence of gonadal hormones during puberty is a major factor in the ability of steroids to activate reproductive and flank marking behavior in adult male hamsters and in androgen receptor expression within the neural circuit underlying these behaviors. Thus, gonadal hormones during puberty appear to exert long‐lasting changes in neural circuits that are responsible for the programming of activational responses to steroids later in adulthood. A two‐stage model for maturation of male social behaviors is proposed: a perinatal critical period for sexual differentiation of neural circuits, followed by the pubertal period, during which gonadal steroids further organize the circuits to enhance behavioral responsiveness to hormones in adulthood. Whether puberty is a critical period for the proposed second wave of steroid‐dependent organization of behavioral circuits remains to be determined.

Testosterone Programs Adult Social Behavior before and during, But Not after, Adolescence

Whereas the adolescent brain is a major target for gonadal hormones, our understanding of hormonal influences on adolescent neural and behavioral development remains limited. These experiments investigated how variations in the timing of testosterone (T) exposure, relative to adolescence, alters the strength of steroid-sensitive neural circuits underlying social behavior in male Syrian hamsters. Experiment 1 simulated early, on-time, and late pubertal development by gonadectomizing males on postnatal d 10 and treating with SILASTIC brand T implants for 19 d before, during, or after adolescence. T treatment before or during, but not after, adolescence facilitated mating behavior in adulthood. In addition, preadolescent T treatments most effectively increased mating behavior overall, indicating that the timing of exposure to pubertal hormones contributes to individual differences in adult behavior. Experiment 2 examined the effects of preadolescent T treatment on behavior and brain regional volumes within the mating neural circuit of juvenile males (i.e. still preadolescent). Although preadolescent T treatment did not induce reproductive behavior in juvenile males, it did increase volumes of the bed nucleus of the stria terminalis, sexually dimorphic nucleus, posterodorsal medial amygdala, and posteroventral medial amygdala to adult-typical size. In contrast, juvenile anterodorsal medial amygdala and ventromedial hypothalamus volumes were not changed by preadolescent T treatment yet differed significantly in volume from adult controls, suggesting that further maturation of these brain regions during adolescence is required for the expression of male reproductive behavior. Thus, adolescent maturation of social behavior may involve both steroid-independent and -dependent processes, and adolescence marks the end of a postnatal period of sensitivity to steroid-dependent organization of the brain.

An association of early puberty with disordered eating and anxiety in a population of undergraduate women and men

Eating and anxiety disorders are more prevalent in females, increase during adolescence, and are associated with early pubertal development. This study examined whether timing of puberty onset is associated with disordered eating and anxiety in a large sample of postpubertal male and female undergraduate students. Self-report questionnaires assessed timing of puberty, disordered eating, anxiety, alcohol use, personality, and sensation seeking. Females scored significantly higher on measures of disordered eating (binge eating, dietary restraint, eating concerns, and weight and shape concerns) and anxiety (state and trait anxiety) than did males. In addition, early maturing women and men scored significantly higher on measures of disordered eating and anxiety than on time or late maturing women and men. Measures of alcohol use, sensation seeking, and personality characteristics differed in males and females but did not vary with pubertal timing. Findings suggest that early puberty is associated with disordered eating and anxiety, and this association may be due to an organizational effect of pubertal hormones. Despite important differences in body fat composition, both males and females experiencing early puberty had an increased incidence of disordered eating. The fact that early puberty was associated with increased eating and anxiety symptoms in both sexes suggests that puberty may influence these symptoms through both biological and psychosocial mechanisms.

Estradiol Increases Female Sexual Initiation Independent of Male Responsiveness in Rhesus Monkeys

Copulation and female initiation of sexual behavior vary across the ovarian cycle, suggesting that female hormonal condition influences female sexual motivation in rhesus monkeys. However, the effects of hormones on female sexual motivation are difficult to identify because male behavior also varies with female hormonal condition. During the nonbreeding season, male rhesus monkeys are sexually unresponsive to females; thus the effects of estradiol treatment on female sexual motivation can be examined independent of male behavior. This study administered estradiol to five ovariectomized females living in a large age-graded social group during the nonbreeding season. The behavior of these females with and without estradiol treatment was compared. Data were collected concurrently on five intact, noncycling, nonpregnant females. Estradiol treatment significantly increased sexual initiation by ovariectomized females toward males without any significant changes in male behavior. Estradiol-treated females also displayed greater sexual initiation than nonpregnant, intact females. Both estrogen and progesterone were important predictors of sexual initiation in females, with progesterone having an inhibitory effect. Endogenous progesterone levels in females were negatively correlated with male contact behavior, suggesting that female attractiveness is reduced by progesterone. This study provides further support for estrogen as the critical steroid increasing female sexual motivation in primates.

Hormones and history: The evolution and development of primate female sexuality

Sexual behavior is required for reproduction in internally fertilizing species but poses significant social and physical risks. Females in many nonprimate species have evolved physical and behavioral mechanisms restricting sexual behavior to when females are fertile. The same hormones producing female fertility also control these mechanisms, assuring that sex only occurs when reproduction is possible. In contrast to nonprimate mammals, hormones do not regulate the capacity to engage in sex infernale anthropoid primates, uncoupling fertility and the physical capacity to mate. Instead, in primates, sexual motivation has become the primary coordinator between sexual behavior and fertility. This dependence upon psychological mechanisms to coordinate physiology with behavior is possibly unique to primates, including humans, and allows a variety of nonphysiological influences, particularly social context, to regulate sexual behavior. The independence between hormonal state and sexual behavior allows sex to be used for social purposes. This complex regulation of primate sexuality develops during adolescence, where female monkeys show both hormonally influenced sexual motivation and socially modulated sexual behavior. We present findings from rhesus monkeys illustrating how social context and hormonal state interact to modulate adolescent and adult sexuality. It is argued that this flexibility in sexual behavior, combined with a tight regulation of sexual motivational systems by reproductive hormones, allows sexual behavior to be used for nonreproductive purposes while still assuring its occurrence during periods of female fertility. The evolutionary pressures that produced such flexibility in sexual behavior remain puzzling, but may reflect the importance of sexuality to primate social attraction and cohesion.

Peak occurrence of female sexual initiation predicts day of conception in rhesus monkeys (Macaca mulatta)

The present study investigated whether peaks in female sexual initiation could accurately predict conception in group-living female rhesus monkeys. Behavioral observations, 4 or 5 days per week in large, stable, social groups of monkeys, provided frequencies of female initiation of proximity, sexual solicitation, mounts, and ejaculations. Since a preovulatory peak in female sexual initiation is likely linked to the preovulatory oestradiol surge, we used the third day after a peak in behavior as the behavioral estimate of conception date. For each pregnancy, an independent estimate of conception date was derived from ultrasound determination of fetal length. Estimates of conception based on female initiation of proximity with adult males were accurate for more than 90% of pregnancies, whereas observation of ejaculations by males predicted conception in fewer than 60% of pregnancies. Behavioral and ultrasound estimates of conception date were highly correlated and differed by less than I day on average. Accordingly, predictions of delivery date based on behavioral estimates of conception date were as accurate as those based on ultrasound-derived estimates. These data suggest that female-initiated sexual behavior can be used in rhesus monkeys as a practical, non-invasive tool for producing timed matings in social groups of monkeys, providing accurate estimates of conception date, gestational age, and predicted date of birth.