Sexual differentiation of the neuroendocrine control of gonadotrophin secretion: concepts derived from sheep models.

In our laboratory the sheep is used as an experimental model to study the early programming of the neuroendocrine mechanisms timing the pubertal increase in GnRH secretion. This interest has arisen because puberty in male lambs occurs much earlier than that in female lambs. Such sex differences in the timing of puberty are present in most species, as well as in the patterns of reproduction in the adult. Although this finding could merely reflect differences in the function of the ovary and testes, many of these differences arise from early sexual differentiation of central mechanisms controlling GnRH secretion. Two models are used for our studies. One model (Model I) has been developed to understand how the male reproductive neuroendocrine system becomes differentiated from that of the female system. The other (Model II) is used to study abnormal female sexual differentiation and the possible aetiologies of reproductive diseases. The discussion focuses on how these two models can be used to study the organizational action of steroids on the mechanisms timing puberty and the secretion patterns of reproductive hormones in the adult. Broadly, our findings indicate that an extended period of steroid action on the developing brain programmes sex differences in GnRH secretion that are manifest later in life: in the expression of pulsatile GnRH release after birth or earlier; in its amplification during puberty; in its differential regulation during young adulthood. Inappropriate programming of the control of GnRH secretion can lead to impaired fertility.