Expression of the IGF System in Human Adrenal Tissues from Early Infancy to Late Puberty: Implications for the Development of Adrenarche

Estrogen Signaling in the Adrenal Cortex

“…Expression decreased at the age of 3 months, when the fetal zone undergoes physiological involution, and increased with adrenarche (at a mean age of 6 years), when the fully developed zona reticularis starts to produce the androgen precursor dehydroepiandrosterone and its sulfate ester, dehydroepiandrosterone sulfate. 106 By contrast, ERα remains undetectable until childhood and puberty. 106 Of note, ERβ immunostaining in the zona reticularis was found in both the cytoplasm and the nucleus.…”

“…106 By contrast, ERα remains undetectable until childhood and puberty. 106 Of note, ERβ immunostaining in the zona reticularis was found in both the cytoplasm and the nucleus. Expression of GPER-1 protein in the adrenal gland, with prominent expression levels in the ZG and the medulla from adrenarche to puberty, was first reported in humans in 2007.…”

“…Expression of GPER-1 protein in the adrenal gland, with prominent expression levels in the ZG and the medulla from adrenarche to puberty, was first reported in humans in 2007. 106,107 In adults, the expression of ERs remained unknown until 2008, when 2 groups independently reported high expression of ERβ and low expression of ERα. 92,108 However, the expression of GPER-1 remained unknown until 2014 when we first detected GPER-1, besides the classic ERs and the recently identified ERα isoform ERα36, in the human adult adrenal cortex.…”

“…The different expression pattern of ERs between APA and normal adrenal cortex, 69,92,106,108 along with the capability of E2 to enhance aldosterone production via GPER-1 during ERβ blockade, 69 suggests cross-talk between GPER-1 and ERβ in the development of high BP and primary aldosteronism. In line with this proposition, it was found that E2 decreases aldosterone levels and the response of aldosterone to angiotensin II in ovariectomized female rats.…”

Adrenarche: Postnatal Adrenal Zonation and Hormonal and Metabolic Regulation

“…However, studies of IGF-I, IGF-II and IGF-R1 mRNA expression and immunolocalization in human adrenals, from early infancy to late puberty, show very low IGF-RI expression in the ZR, suggesting that the IGF system is not directly involved in the regulation of adrenal androgen via ZR cells. Therefore, it has been proposed that IGF-I and perhaps IGF-II are involved at another level, either by autocrine, paracrine or endocrine stimulation, in the postnatal mechanisms of progenitor adrenal cell proliferation and migration [26]. Although circulating and tissue IGF-II levels are highest during fetal life and decrease postnatally, a postnatal role of IGF-II in the adrenal gland cannot be discarded.…”