Estrogen-IGF-1 interactions in neuroprotection: Ischemic stroke as a case study

Abstract

The steroid hormone 17b-estradiol and the peptide hormone insulin-like growth factor (IGF)-1 independently exert neuroprotective actions in neurologic diseases such as stroke. Only a few studies have directly addressed the interaction between the two hormone systems, however, there is a large literature that indicates potentially greater interactions between the 17b-estradiol and IGF-1 systems. The present review focuses on key issues related to this interaction including IGF-1 and sex differences and common activation of second messenger systems. Using ischemic stroke as a case study, this review also focuses on independent and cooperative actions of estrogen and IGF-1 on neuroprotection, blood brain barrier integrity, angiogenesis, inflammation and post-stroke epilepsy. Finally, the review also focuses on the astrocyte, a key mediator of post stroke repair, as a local source of 17b-estradiol and IGF-1. This review thus highlights areas where significant new research is needed to clarify the interactions between these two neuroprotectants.

Why estrogens matter for behavior and brain health

“…Both 17β-estradiol and IGF-1 regulate common second messenger systems that are critical for disease process such as cell survival and angiogenesis (Sohrabji, 2014). 17β-estradiol and IGF-1 are critical mitogens, and the PI3K-AKT-mTOR pathway appears to be the principal transducer of their actions.…”

Regulation of astroglia by gonadal steroid hormones under physiological and pathological conditions

“…The main hormonal action of sex steroids in the brain is the regulation of reproduction and neuroendocrine secretions. In addition to these hormonal actions, gonadal steroids exert trophic effects on neural cells, which contribute to the maintenance of neural tissue homeostasis, to the regulation of synaptic plasticity and synaptic function; as well as to promoting neuronal survival and neural repair under pathological conditions (see (Arevalo et al, 2015;Guennoun et al, 2015;Sohrabji, 2015;Vest and Pike, 2013) for recent reviews). Sex steroids are also synthesized in other tissues including the nervous tissue, which brought the important idea of considering the CNS as a steroidogenic tissue (do Rego and Vaudry, 2015;Sinchak et al, 2003;Zwain and Yen, 1999).…”

Astrocytic response to cerebral ischemia is influenced by sex differences and impaired by aging

“…Astrocytes synthesize and release IGF-1 and therefore may play an important role in neuroprotection, in view of the beneficial effects reported for this growth factor in stroke (Sohrabji, 2015). Recently it was shown that astrocytes protect neurons from oxidative stress induced by H 2 O 2 and this neuroprotection is abrogated with blockade of the IGF-1 receptor in astrocytes (Genis et al, 2014).…”