Infertility is becoming a major public health problem, with increasing frequency due to medical, environmental and societal causes. The increasingly late age of childbearing, growing exposure to endocrine disruptors and other reprotoxic products, and increasing number of medical reproductive dysfunctions endometriosis, polycystic ovary syndrome, etc. Fertility relies on fine-tuned control of both neuroendocrine function and reproductive behaviors, those are critically regulated by sex steroid hormones.
Testosterone and estradiol exert organizational and activational effects throughout life to establish and activate the neural circuits underlying reproductive function. This regulation is mediated through estrogen receptors ERs and androgen receptor AR. Particular emphasis will be placed on the neural role of these receptors and the underlying sex differences.
In mammals, fertility allows the perpetuation of the species. Fertility relies on a fine regulation of reproductive function involving both adequate neuroendocrine regulation of the hypothalamic-pituitary-gonadal HPG axis, and synchronized expression of male and female sexually dimorphic reproductive behaviors. Within the HPG axis, the pulsatile release of gonadotropin releasing hormone GnRH from hypothalamic GnRH neurons in the hypothalamic-pituitary portal system activates the neuroendocrine secretion of the gonadotropins luteinizing hormone LH and follicle-stimulating hormone FSH Figure 1.
LH and FSH stimulate the gonads and trigger gametogenesis and secretion of gonadal steroid hormones. Sex steroid hormones in turn exert a feedback control on the HPG axis 1. In males, testicular testosterone exerts a negative feedback control on hypothalamic GnRH and pituitary LH release 2. In females, estradiol negatively regulates hypothalamic GnRH secretion for most of the estrous cycle, except during the proestrus phase. During this phase, the growth of ovarian follicles is associated with a rise in circulating estradiol concentration that exerts hypothalamic and pituitary positive feedbacks, leading to the LH discharge necessary for ovulation and induction of female receptivity 3 , 4.
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GnRH neurons activity is finely regulated by a complex neural network including kisspeptin-, neurokinin B-, glutamate- and GABA-expressing neurons. Glial cells, especially astrocytes and tanycytes, also participate in this regulation 5.
