The effect of adrenarche on the reproductive axis
Adrenarche is a developmental process almost unique to humans in which the adrenal glands produce high levels of dehydroepiandrosterone (DHEA) ~2-3 years before puberty. Although the function of adrenarche is not known, premature adrenarche often leads to early puberty and polycystic ovarian syndrome (PCOS). We hypothesized that these DHEA effects involve epigenetic modification. We examined DNA methylation levels in proxy tissues from a large cohort of children, and found levels around several puberty and PCOS-related genes were linked to DHEA levels. We then used a novel animal model for adrenarche, the spiny mouse, to investigate changes in gene expression in reproductive tissues during their natural adrenarche-like state, and after prepubertal adrenalectomy (ADX) and DHEA rescue. Our findings provide new insights into how DHEA affects the reproductive axis maturation leading up to puberty, and at high levels may predispose to PCOS.
