Transcription Factor GATA-6 in the Human Adrenocortex: Association with Adrenal Development and Aging

Abstract

Abstract. Transcription factor GATA-6 has been demonstrated to be expressed in the human fetal and adult adrenal cortex and has been postulated to play an important role in adrenal steroid biosynthesis. However, the status for GATA-6 expression has not been examined in detail especially in relation to adrenal development and aging. Therefore, in this study, we analyzed GATA-6 expression in 11 human fetal adrenals and 19 adrenal glands after birth using immunohistochemistry. In the fetal adrenals, the status of GATA-6 immunoreactivity in the definitive zone was significantly and directly correlated with ages of development (P<0.05) but in the fetal zone was significantly and inversely correlated with ages of development (P<0.05). After birth, GATA-6 was more abundant in the zona fasciculata compared to other zones (P<0.05) but was not related to aging of the subject. These results suggest that GATA-6 expression is involved in the regulation of corticosteroid production in both the human fetal and adult adrenals, and the changes of intra-adrenal GATA-6 expression in the human fetal adrenal plays important roles in developmental changes of both the definitive and fetal zones.

Regulation of adrenocortical steroid hormone production by RhoA–diaphanous 1 signaling and the cytoskeleton

“…For example, the transcription of genes that are required for the uptake and transport of cholesterol and for its metabolism into cortisol and aldosterone requires several transcription factors (Miller and Auchus, 2011, Rainey and Nakamura, 2008, Sewer et al, 2007, Sewer et al, 2008), including steroidogenic factor 1 (El-Khairi et al, 2011, Hoivik et al, 2010, Schimmer and White, 2010), nerve growth factor 1B (Bassett et al, 2004, Bassett et al, 2004), members of the specificity protein family (e.g. Sp1, Sp3) (Huang et al, 2005, Lin et al, 2001, Rui et al, 2008), sterol regulatory element binding protein 1 (Ozbay et al, 2006), GATA proteins (Fluck and Miller, 2004, Jimenez et al, 2003, Nakamura et al, 2007), and cAMP response element modulator (Meier and Clark, 2012, Sugawara et al, 2006, Zwermann et al, 2007). Moreover, emerging evidence implicates the need for the assembly of macromolecular protein complexes that facilitate the movement of cholesterol into the inner mitochondrial membrane (Bose et al, 2002, Bose et al, 2008, Liu et al, 2006, Rone et al, 2012) and for regulatory mechanisms that govern the selective transfer of electrons (Miller, 2005).…”

GATA6, SF1, NGFIB and DAX1 in the remodeled subcapsular zones in primary aldosteronism

“…These important transcription factors have been all previously reported in human adrenal cortex but their possible involvement in the remodeled subcapsular zones of both IHA and APA adjacent adrenal gland has remained unknown [13][14][15][16][17]. Therefore, in this study, we immunolocalized GATA6, SF1, NGFIB and DAX1 in the remodeled sub-capsular zones of IHA and APA associated adrenal glands and compared these results with staining in the zona glomerulosa (ZG) of normal adrenal tissues in order to obtain the better understanding of these unique and interesting features of subcapsular zones of the adrenals associated with PA.…”

GATA factors in endocrine neoplasia

“…Postnatally, expression of Gata6 in the mouse adrenal is limited to capsular and subcapsular cells (Pihlajoki et al, 2013). In primates, GATA6 is expressed in the zona reticularis, where it is thought to regulate androgen biosynthesis (Jimenez et al, 2003; Nakamura et al, 2007; Nakamura et al, 2009). By comparison, GATA4 has a more restricted pattern of expression during adrenocortical development and is presumed to have a more limited role in the function of this organ (Kiiveri et al, 2002).…”