Prenatal programming of the female reproductive neuroendocrine system by androgens

Abstract

It has been clear for several decades that the areas of the brain that control reproductive function are sexually dimorphic and that the ‘programming actions’ of the male gonadal steroids are responsible for sex-specific release of the gonadotrophins from the pituitary gland. The administration of exogenous steroids to fetal/neonatal animals has pinpointed windows of time in an animals’ development when the reproductive neuroendocrine axis is responsive to the organisational influences of androgens. These ‘critical’ periods for sexual differentiation of the brain are trait- and species-specific. The neural network regulating the activity of the gonadotrophin releasing hormone (GnRH) neurones is vital to the control of reproductive function. It appears that early exposure to androgens does not influence the migratory pathway of the GnRH neurone from the olfactory placode or the size of the population of neurones that colonise the postnatal hypothalamus. However, androgens do influence the number and the nature of connections that these neurones make with other neural phenotypes. Gonadal steroid hormones play key roles in the regulation of GnRH release acting largely via steroid-sensitive intermediary neurones that impinge on the GnRH cells. Certain populations of hormonally responsive neurones have been identified that are sexually dimorphic and project from hypothalamic areas known to be involved in the regulation of GnRH release. These neurones are excellent candidates for the programming actions of male hormones in the reproductive neuroendocrine axis of the developing female.