Abstract
The second-to-fourth digit ratio (2D:4D ratio) is considered a postnatal proxy measure for the degree of prenatal androgen exposure (PAE), which is the primary factor responsible for masculinizing the brain of a developing fetus. Some studies suggest that the organizational effects of PAE may extend to the hypothalamic-pituitary-adrenal (HPA) axis response to stress. This study investigates the relationship between 2D:4D ratio and HPA axis functioning using a rhesus monkey (Macaca mulatta) model. Subjects were N = 268 (180 females, 88 males) rhesus monkey infants (3–4 months of age). Plasma cortisol concentrations were assayed from two blood samples obtained during a 25-h experimental social separation stressor at 2- and 7-h post-separation. Subjects’ 2D:4D ratio was measured later in life (Mage = 6.70 years). It was hypothesized that infant rhesus monkeys that exhibited a more masculine-like 2D:4D ratio would show lower levels of circulating cortisol after a social separation and relocation stressor. The results showed that there was a sex difference in the left-hand 2D:4D ratio. The results also showed that there was an overall sex difference in cortisol concentrations and that female, but not male, monkeys that exhibited a more masculine-like right- and left-hand 2D:4D ratio exhibited lower mean stress-induced cortisol concentrations early in life. These findings suggest that higher levels of prenatal androgens in females, as measured by 2D:4D ratio, may be related to an attenuated HPA axis stress-response, as measured by plasma cortisol levels. To the extent that these findings generalize to humans, they suggest that the organizational effects of PAE extend to the infant HPA axis, modulating the HPA axis response, particularly in females.
Highlights
Prenatal androgen exposure (PAE) is thought to be the main source of morphological and central nervous system masculinization, and, is responsible for many of the phenotypic behavioral differences observed between males and females (Phoenix et al, 1959; Hughes, 2001; Thornton et al, 2009)
Partial support was found for the hypotheses: There was a relationship between circulating stress-response plasma cortisol and 2D:4D ratio in females, with females that possessed a more male-typical 2D:4D ratio exhibiting lower plasma cortisol concentrations as infants during a mother-infant social separation stressor
To the extent that the 2D:4D ratio is a biomarker for the degree of PAE, these results suggest that PAE has a prenatal organizational effect on the HPA axis, which appears to attenuate the stress response of the HPA axis in female rhesus monkeys
Summary
Prenatal androgen exposure (PAE) is thought to be the main source of morphological and central nervous system masculinization, and, is responsible for many of the phenotypic behavioral differences observed between males and females (Phoenix et al, 1959; Hughes, 2001; Thornton et al, 2009). The degree of PAE varies between the sexes (males typically have a higher degree of PAE; Wilson et al, 1981), but there are wide individual differences within each of the sexes. Studies show that variation in PAE contributes to stable individual differences in brain function and behavior (Hines et al, 2016; Spencer et al, 2017; Del Giudice et al, 2018). PAE plays a complex and important modulating role in the development of typical sex differences through its organizational effect on the brain. Studies show that PAE is implicated in the development of several psychopathological disorders with extant sex differences in incidence rates, such as autism spectrum disorder (Cherskov et al, 2018), schizophrenia (Paipa et al, 2018), attention deficit hyperactive disorder (Martel et al, 2008) and, relevant to this study, anxiety disorders (de Bruin et al, 2006)
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