Pubertal development and regulation

Abstract

Puberty marks the end of childhood and is a period when individuals undergo physiological and psychological changes to achieve sexual maturation and fertility. The hypothalamic-pituitary-gonadal axis controls puberty and reproduction and is tightly regulated by a complex network of excitatory and inhibitory factors. This axis is active in the embryonic and early postnatal stages of life and is subsequently restrained during childhood, and its reactivation culminates in puberty initiation. The mechanisms underlying this reactivation are not completely known. The age of puberty onset varies between individuals and the timing of puberty initiation is associated with several health outcomes in adult life. In this Series paper, we discuss pubertal markers, epidemiological trends of puberty initiation over time, and the mechanisms whereby genetic, metabolic, and other factors control secretion of gonadotropin-releasing hormone to determine initiation of puberty.

Figure 1. Physical changes and secondary sexual characteristics that appear during pubertal development

Changes in body composition are used to detect pubertal development. The figure shows the physical changes that occur as a result of the activation of the hypothalamic-pituitary-gonadal axis.

Figure 2. Mechanisms of action of the genetic factors involved in the control of puberty onset

Important regulators of GnRH have been identified in patients with pubertal disorders. The figure depicts essential regulators of GnRH secretion in which mutations have been identified in human beings. Dashed line represents proposed pathway. FSH=follicle-stimulating hormone. GnRH=gonadotropin-releasing hormone. GnRHR=gonadotropin-releasing hormone receptor. KISS1=kisspeptin. KISS1R=kisspeptin receptor. LH=luteinising hormone. MKRN3=makorin ring finger protein 3. NKB=neurokinin B. NK3R=neurokinin B receptor. +=stimulatory effect. –=inhibitory effect. ?=proposed mechanism.

Figure 3

Tentative model for the metabolic control of GnRH secretion by peripheral metabolic hormones The peripheral hormones that transmit metabolic signals to GnRH neurons are shown: leptin, a signal for energy abundance, is a permissivefactor for GnRH secretion. Ghrelin, a putative signal of energy insufficiency, is an inhibitory factor for GnRH secretion. Insulin and IGF-1 have stimulatory effects on the reproductive axis. Dashed line represents proposed pathway. FSH=follicle-stimulating hormone. GnRH=gonadotropin-releasing hormone. GnRHR=gonadotropin-releasing hormone receptor. IGF-1=insulin-like growth factor 1. KISS1=kisspeptin. KISS1R=kisspeptin receptor. LH=luteinising hormone. +=stimulatory effect. –=inhibitory effect.