DHEAS and Human Development: An Evolutionary Perspective

Abstract

Adrenarche, the post-natal rise of DHEA and DHEAS, is unique to humans and the African Apes. Recent findings have linked DHEA in humans to the development of the left dorsolateral prefrontal cortex (LDPFC) between the ages of 4-8 years and the right temporoparietal junction (rTPJ) from 7 to 12 years of age. Given the association of the LDLPFC with the 5-to-8 transition and the rTPJ with mentalizing during middle childhood DHEA may have played an important role in the evolution of the human brain. I argue that increasing protein in the diet over the course of human evolution not only increased levels of DHEAS, but linked meat consumption with brain development during the important 5-to-8 transition. Consumption of animal protein has been associated with IGF-1, implicated in the development of the adrenal zona reticularis (ZR), the site of DHEAS production. In humans and chimps, the zona reticularis emerges at 3-4 years, along with the onset of DHEA/S production. For chimps this coincides with weaning and peak synaptogenesis. Among humans, weaning is completed around 2 ½ years, while synaptogenesis peaks around 5 years. Thus, in chimpanzees, early cortical maturation is tied to the mother; in humans it may be associated with post-weaning provisioning by others. I call for further research on adrenarche among the African apes as a critical comparison to humans. I also suggest research in subsistence populations to establish the role of nutrition and energetics in the timing of adrenarche and the onset of middle childhood.

Validation of a Dehydroepiandrosterone-Sulfate Assay in Three Platyrrhine Primates (Alouatta caraya, Aotus azarae infulatus, and Sapajus apella)

“…To better understand the functions and age-related patterns of DHEAS secretion and excretion in primate evolution, comparative research involving platyrrhines is needed. These studies may help us to develop platyrrhine models for studying the effects of DHEAS on cognition and neonatal development, age-related disorders, and on the evolution of the adrenal gland among primate species (Campbell, 2020;Takeshita et al, 2018b). Furthermore, the GC/DHEAS index can be used as part of a multifaceted and more accurate assessment of stress (Takeshita et al, 2019;Whitham et al, 2020) and can be applied to monitor primate welfare and reproduction.…”

The timing of adrenarche in Maya girls, Merida, Mexico

“…Campbell (2020) suggests that, given neurological functions of DHEA‐S, rising adrenarcheal levels are crucial for cortical maturation and synaptic modification which translate phenotypically into increased competencies in middle childhood. He proposes that adrenarche might be a developmental pathway through which increased meat consumption contributed to brain expansion during Homo evolution.…”

The Enigma of the Adrenarche: Identifying the Early Life Mechanisms and Possible Role in Postnatal Brain Development

“…The intention of this article is to discuss the possible physiological mechanisms that initiate and support the hormonal changes that characterize adrenarche in humans and some non-human primates. As such, we have not attempted a systematic review of this topic; such a review has been done expertly in recent times [ 1 , 2 , 3 , 4 ]. We will also suggest what could be done if a tractable, small animal model of the adrenarche could be found.…”

“…Hence, why the mechanistic understanding of adrenarche—in particular, the origin of the factors that drive the dynamic changes within a strictly defined zone of the adrenal cortex, the ZR—is still poorly defined and essentially unknown. Similarly, there has been much discussion around the impact on the brain of adrenarche and the associated increase of DHEA during human adolescence and adult life [ 1 ]. Notwithstanding the important evolutionary perspective pointed out by Campbell [ 1 ], the mechanistic aspects of adrenarche remain highly speculative, not least because of the practical and ethical limitations of conducting experiments that dissect the essential mechanisms of humans and primates.…”

“…Similarly, there has been much discussion around the impact on the brain of adrenarche and the associated increase of DHEA during human adolescence and adult life [ 1 ]. Notwithstanding the important evolutionary perspective pointed out by Campbell [ 1 ], the mechanistic aspects of adrenarche remain highly speculative, not least because of the practical and ethical limitations of conducting experiments that dissect the essential mechanisms of humans and primates. The absence of a clearly defined adrenarche in commonly used laboratory animals—rats and conventional mice synthesize little DHEA in the adrenal gland and brain [ 12 , 14 , 15 , 16 ]—contributes to our poor understanding of what initiates and controls the change of adrenal function before puberty in humans.…”