Sonic hedgehog signaling during adrenal development

Abstract

It has been speculated for a number of years that Sonic hedgehog (Shh) signaling plays an important role in adrenal development. Over the past two years several reports have described the expression and function of Shh pathway genes in the adrenal cortex, using primarily mouse models. The key findings are that Shh signals produced by a population of partially differentiated cortical cells located in the outer cortex/zona glomerulosa are received by non-cortical mesenchymal cells located predominantly in the overlying capsule. This signal is required for growth of both the capsule and the cortex, but not for cortical zonation or steroidogenic cell differentiation. Using molecular genetic tools to define the adrenocortical cell lineages that are descended from both Shh signaling and receiving cells, both capsule and cortical cells were found to have properties of adrenocortical stem and/or progenitor cells. Here we place these observations within the context of prior studies on adrenal development, postnatal adrenal maintenance and adrenocortical stem/progenitor cell lineages.

Fgfr2 is required for the expansion of the early adrenocortical primordium

“…The fetal zone regresses after puberty in mice while the definitive cortex subdivides in a thin outer zona glomerulosa synthesizing mineralocorticoids and a thick inner zona fasciculata producing glucocorticoids. Homeostasis of the adrenal cortex is mediated by capsular and subcapsular progenitors that give rise to steroidogenic cells that move centripetally (for reviews see Laufer et al, 2012;Walczak and Hammer, 2015).…”

Ectopic expression of Sonic Hedgehog in a cryptorchid man with azoospermia: A case report

“…11 Moreover, in the testis, studies have demonstrated that Sf-1 is also produced by the Sertoli and Leydig cells. 8 Sf-1 has been shown to regulate the synthesis and secretion of steroid hormone (androgen) through directing the expression of steroidogenic enzymes, such as steroidogenic acute regulatory cytochrome P450, to produce testosterone.…”

A expressão dos marcadores de células-tronco, SF1 e DAX1 no desenvolvimento do córtex adrenal humano e sua associação com a via Wnt/beta-catenina na tumorigênese adrenocortical

“…LOH, rearrangements and abnormal imprinting of the 11p15.5 locus, resulting in increased IGF2 expression and decreased p57kip2 and H19 expression, have frequently been found in sporadic ACTs [143][144][145].…”

“…IGF2 mRNA expression is increased in 8.5 and 90% of adult ACAs and ACCs, respectively. In adult patients, but not in pediatric patients, IGF2 overexpression was associated with unfavorable outcome and increased recurrence risk [5,15,[144][145][146].…”

“…They also identified IGF1R, which is an IGF2 receptor, as a pediatric ACC marker [145]. Subsequently, preclinical studies were developed using IGF1R antagonists as a therapeutic approach to inhibit ACC growth in humans [145,147]. From these data, a Phase I clinical trial has been developed using 'figitumumab' (CP-751 871), a monoclonal antibody that prevents IGF1R activation blocking IGF1 and IGF2 binding.…”