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Review
. 2018 Aug;30(4):532-540.
doi: 10.1097/MOP.0000000000000642.

Genetics of pubertal timing

Jia Zhu  1 , Temitope O Kusa  2 , Yee-Ming Chan  1   2
Affiliations
Review

Genetics of pubertal timing

Jia Zhu et al. Curr Opin Pediatr. 2018 Aug.

Abstract

Purpose of review: To summarize advances in the genetics underlying variation in normal pubertal timing, precocious puberty, and delayed puberty, and to discuss mechanisms by which genes may regulate pubertal timing.

Recent findings: Genome-wide association studies have identified hundreds of loci that affect pubertal timing in the general population in both sexes and across ethnic groups. Single genes have been implicated in both precocious and delayed puberty. Potential mechanisms for how these genetic loci influence pubertal timing may include effects on the development and function of the GnRH neuronal network and the responsiveness of end-organs.

Summary: There has been significant progress in identifying genetic loci that affect normal pubertal timing, and the first single-gene causes of precocious and delayed puberty are being described. How these genes influence pubertal timing remains to be determined.

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Conflict of interest statement

Conflicts of Interest

Y.-M.C. delivered a presentation on the genetics of pubertal timing at an unrestricted educational symposium sponsored by Endo Pharmaceuticals held at the International Meeting of Pediatric Endocrinology in September 2017.

Figures

Figure 1
Figure 1. (Original) Putative sites of action for genes implicated in precocious puberty, normal variation in pubertal timing, and delayed puberty
Select genes are listed next to their likely sites of action within the hypothalamic-pituitary-gonadal axis. Of note, some genes implicated in precocious puberty (DLK1, MKRN3, and KISS1) and in delayed puberty (TACR3) are also associated with variation in normal pubertal timing, indicated by underlining.
Figure 2
Figure 2. (Original) Potential mechanisms underlying variation in pubertal timing
The graph schematizes the hormonal and physical events that mark pubertal onset and shows potential mechanisms for variation in pubertal timing. The solid black curve in panel A represents typical hormone production over time, with a period of robust activity in infancy (“minipuberty”), a relative quiescence in childhood, and reemergence of activity at puberty. The dashed line represents the “threshold” concentration of gonadotropins and/or sex-steroids needed for the appearance of physical signs of puberty, such as testicular growth in males and thelarche in females. These physical signs appear when hormonal activity reaches the threshold, indicated by the circle. Three potential mechanisms for variation in pubertal timing are illustrated in Panels B–D. The solid black curve depicts normal pubertal timing. Variations resulting in differences in pubertal timing are depicted in gray; these include variation in the timing of activation of the GnRH neuronal network (B), in the rate of rise of gonadotropins/sex-steroids (C), and in end organ responsiveness to gonadotropins and/or sex steroids (D). These mechanisms are not mutually exclusive.
See this image and copyright information in PMC

References

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