Maturation and physiology of hypothalamic regulation of the gonadal axis

Abstract

In mammals, maturation of the gonadal axis at puberty appears to be timed by an increase in tonic gonadotropin release from the anterior lobe of pituitary gland, where the synthesis and release of gonadotropins, such as the follicle-stimulating hormone and luteinizing hormone, are stimulated by the gonadotropin-releasing hormone (GnRH) released from the hypothalamus. The concept of hypothalamic regulation of the gonadal axis dates back to the middle of last century, and our understanding for the GnRH/gonadotropin-releasing system has become abundantly clearer from studies in the last few decades or so. To date, the most plausible interpretation is that KNDy neurons, which produce kisspeptin, neurokinin B, and dynorphin A, serve as a master regulator of tonic GnRH/gonadotropin release, which governs the pubertal maturation of gonadal activity, i.e., gametogenesis and steroidogenesis. Estrogen derived from the immature ovary appears to play a critical role in prepubertal restraint of kisspeptin biosynthesis and hence GnRH/gonadotropin release in rodents and sheep. Decreased sensitivity to estrogen negative feedback during the pubertal transition is likely a key event for pubertal maturation of the hypothalamic mechanism regulating GnRH and then gonadal activity. It is noteworthy that steroid dependency differs from species to species. In primates, steroid-independent inhibition is mainly underlying the prepubertal restraint of GnRH/gonadotropin-releasing system. In all mammalian species, the timing of puberty onset is dependent on body weight rather than chronological age. Thus, hypothalamic mechanisms underlying the relationship between nutritional statuses and relieving the prepubertal restraint of kisspeptin biosynthesis are still unanswered questions.