Sensitive Periods for Hormonal Programming of the Brain

Abstract

During sensitive periods, information from the external and internal environment that occurs during particular phases of development is relayed to the brain to program neural development. Hormones play a central role in this process. In this review, we first discuss sexual differentiation of the brain as an example of hormonal programming. Using sexual differentiation, we define sensitive periods, review cellular and molecular processes that can explain their restricted temporal window, and discuss challenges in determining the precise timing of the temporal window. We then briefly review programming effects of other hormonal systems and discuss how programming of these systems interact with sexual differentiation.

Perinatal Exposure to Bisphenol-A Impairs Spatial Memory through Upregulation of Neurexin1 and Neuroligin3 Expression in Male Mouse Brain

“…It has been well established that certain periods during development such as embryonic stage, early postnatal life and juvenile stage are critically susceptible to BPA exposure [53] . The levels of endogenous hormones all through the developmental period are essential for regulating the sexual differentiation of brain and behavior [54] . Growing body of studies has established the effect of perinatal exposure to BPA on memory impairment [13] , [55] .…”

Cognitive abilities in women with complete androgen insensitivity syndrome and women with gonadal dysgenesis

“…Activity in these systems has three peaks in human development: early during gestation, post partum, also refered to as "minipuberty" and in puberty. Increases in sex typical hormones and subsequent decreases induced by feedback mechanisms, create a hormonal milieu that directs the individual's general body growth, the development of genitalia in particular, sex characteristics, and also aspects of brain development (22). Further on, pregnancy and menopause also constitute periods of considerable systemic change in the hormonal situation.…”

“…In experimental research different models exist to explain the mechanisms behind these phenomena. Periodical sensitivity and increasing resistance to sex hormones is one such mechanism, (25) epigenetic changes another, (22) to understand periods where development accelerates or occur in response to exposure and modulating effects of sex hormones. Most babies born are assigned to either sex by assessment of their genitals at birth or by ultrasound during gestation.…”

“…Androgens play a crucial role for prenatal genital development, and the brain is also influenced by the fluctuations in sex hormone levels but while genital development has a sensitive window during the first half of gestation, the entire period from before birth to around puberty has been suggested to constitute a sensitive period for brain development (22). Most research done hitherto on critical periods was carried out in animals and the evidence in humans for sensitive/critical periods either regarding gender role behavior, gender identity or sexual preferences is scarce and understudied.…”

Progesterone from maternal circulation binds to progestin receptors in fetal brain

“…Steroid hormones exert profound effects on the maturation of the nervous system through the activation of nuclear receptors which, as transcription factors, can influence fundamental mechanisms of neural development. This has been most notably demonstrated in the ability of the fetal gonadal hormone testosterone and its metabolites to produce marked and permanent sex differences in brain structure and function [for recent reviews see (Lenz et al, ; de Vries et al, )]. However, it is becoming increasingly clear that the developing brain is also sensitive to progestins during critical periods of maturation (Quadros et al, ; Lopez and Wagner, ; Jahagirdar and Wagner, ) and that progesterone may play a previously underappreciated role in neural development.…”