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Abstract

1. There are numerous sites in the nervous system where steroid hormones dramatically influence development. Increasing interest in mechanisms in neural development is providing avenues for understanding how gonadal steroids alter the ontogeny of these regions during sexual differentiation. 2. An increasing number of researchers are examining effects of gonadal steroids on neurite outgrowth, cell differentiation, cell death, cell migration, and synaptogenesis. The interrelated timing of these events may be a key aspect influenced by gonadal steroids throughout development. 3. The preoptic area and hypothalamus are characteristically heterogeneous in terms of cell type (e.g., different neuropeptides) and cell derivation. Perhaps a major reason for the ontogeny of sexual differences in the preoptic area and hypothalamus lies in the convergence of many different cell types from diverse sources (i.e., proliferative zones surrounding the lateral and third ventricles, and the olfactory placodes) that can be influenced in an interactive manner by gonadal steroid mechanisms. 4. The characterization of multiple mechanisms (e.g., trophic, migratory, apoptotic, fate, etc.,) that contribute to permanent changes in brain structure and ultimately function is essential for unraveling the process of sexual differentiation.

Prenatal maternal immune disruption and sex-dependent risk for psychoses

“…It is likely that multiple mechanisms regulate the effects of cytokines on offspring brain development, with specific mechanisms depending on timing of exposure. These include: dysregulation of nerve growth factors (Schobitz et al 1993; Anisman & Merali, 2002; Gilmore et al 2003; Twohig et al 2011); loss of dendritic connections (Marx et al 2001; Gilmore et al 2004; Twohig et al 2011) and white matter connectivity (Yoon et al 1996; Dammann & Leviton, 1997); apoptosis (Hu et al 1997); dysregulation of neurotransmitters (Zalcman et al 1994; Behrens et al 2008); and hormonal dysregulation (Schobitz et al 1993; Anisman & Merali, 2002) impeding healthy sexual differentiation of the brain (Handa et al 1994; Kawata, 1995; Tobet & Hanna, 1997; Goldstein et al 2001; Tobet, 2002) and brain aging (Zietz et al 2001). …”

Effect of Androgens on Sexual Differentiation of Pituitary Gamma-Aminobutyric Acid Receptor Subunit GABA_B Expression

“…Sexual differences may be manifested after the critical period of hormonal action has elapsed and high steroid levels are no longer present [52, 53], as in sexual differences in gonadotropin secretion [30]. In contrast, many characteristics cannot be differentiated by sex in adulthood because these sex differences are present only transiently during development [32, 54]. For example, around birth, male rats express much higher levels of progesterone receptor in the medial preoptic area than do females; this sex difference starts to disappear once the ovaries become active [55].…”

“…Sexually dimorphic differences in neuronal connections and brain structures are the result of the irreversible action of gonadal hormones during a sensitive period [31, 32]. In rats, androgens secreted both prenatally by fetal testis (E-18) and early postnatally [33]permanently masculinize and defeminize neural substrates, controlling sexually dimorphic brain functions, behavior and genital morphology [29, 30, 34, 35].…”

Sex differences in the brain–an interplay of sex steroid hormones and sex chromosomes

“…These structural differences, leading to sex differences in behaviour, are spread throughout the nervous system rather than concentrated in a single structure or a system. Sex differences were initially found in the hypothalamus, one of the most sexually dimorphic areas of the brain [64][65][66][67]. One of the first observed sexual dimorphic areas was the preoptic area of the hypothalamus, more precisely the medial preoptic area (MPOA), part of the brain that regulates reproductive behaviours [15,68].…”