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Reversal of HPA response to oestrogen around puberty

10 Jul 2009


Puberty is a critical period during which gonadal steroids activate numerous adult-specific physiological and neurobehavioural traits. Previous studies have provided evidence of a pubertal maturation of the hypothalamo-pituitary-adrenal (HPA) axis in female rats. Specifically it was shown that prepubertal rats take longer than adults to terminate an endocrine response to an acute stressor suggesting that the negative-feedback mechanisms regulating the HPA axis undergo a maturational process during puberty.

The pubertal maturation of the hypothalamo-pituitary-gonadal (HPG) axis ultimately results in stimulation of gonadal steroid production and release, which in turn governs numerous secondary sexually dimorphic processes and characteristics. Research has shown that in rodents, the regions of the brain known to govern HPA activity in adulthood may be capable of responding to oestrogen before puberty; thus the rise in gonadal steroids over puberty may be crucial for the activation of a selection of female neuroendocrine and behavioural traits.

Evuarherhe et al., address an interesting new question: how do estrogens during the peripubertal period influence pituitary-adrenal activity? They carried out studies to investigate whether HPA activity responded to exogenous oestrogen in prepubertal females and whether ovarian activity during puberty had an organizational effect on the adult HPA axis. The authors show that estrogens administered during the peripubertal period attenuate ACTH and corticosterone responses to stress, in contrast to the well-known stimulatory actions of estrogens on HPA axis activity monitored during adulthood.

Their research further suggests that there are two critical times for the organisational programming of an adult HPA response to physiological levels of oestrogen. First there is the neonatal period during which it appears that exposure to sex steroids can programme adult HPA activity and also puberty during which time a non-sex steroid dependent maturational process takes place allowing the development of a stimulatory effect of oestrogens on HPA activity. Evuarherhe, O., Leggett, J., Waite, E., Kershaw, Y, Lightman, S. Journal of Endocrinology, May 2009 DOI:10.1677/JOE-09-0175