Hypothalamic Astrocytes and the Role of Neuroprogesterone in Estrogen Positive Feedback

Astrocytes are critical for the CNS control of female reproduction by mediating estrogen positive feedback-an event through which the hypothalamus controls the surge release of luteinizing hormone (LH) to induce ovulation and the formation of the corpus luteum. Estradiol controls physical interactions between astrocytes and gonadotropin-releasing hormone (GnRH) neurons, controlling synaptic input and peptide release. Importantly, estradiol stimulates astrocytes to release neuroprogesterone, which activates kisspeptin neurons that control GnRH neuronal activity. Like estrogen positive feedback, estradiol-induced neuroprogesterone synthesis appears only in females after puberty. Coincident with the maturation of the reproductive system during puberty, a new population of astrocytes is added to the hypothalamus. It is thought that during estrogen positive feedback, estradiol induces progesterone receptors in kisspeptin neurons, which are activated by estradiol-facilitated neuroprogesterone release from newly born hypothalamic astrocytes. Kisspeptin release then triggers GnRH release, inducing the surge secretion of LH.