Insulin Sensitivity & Estrogen: Regulators of Adrenal Androgens?

Alicia Belgorosky, MD, PhD, of the Endocrine Service at Hospital de Pediatria in Buenos Aires, Argentina, presented findings of research conducted by her and colleagues on the regulation of adrenal androgens.

Though the presentation was a bit too rapid-fire to catch the information on every slide, here are Belgorosky’s research highlights:

The mechanism of cell renewal and structure maintenance of the adult adrenal cortex remains unknown, though proliferative activity (the zonal hypothesis) and cell migration are suspected causes.

There is evidence that the IGF system and insulin might modulate the adult adrenal cortex.

The GH/IGF-I axis and insulin resistance might be involved in the mechanism of adrenarche during prepuberty in normal girls, but not in normal boys

Belgorosky and co. proposed that prepubertal ovarian estrogen might be responsible for the sex difference. Data suggests insulin might be involved in regulation of androgen synthesis after adrenarche takes place.

Adrenarche Hypothesis

1. Peripheral or local IGF-1 might be involved in the regulation adrenal progenitor cell proliferation and migration.
2. Estrogens, among other factors, could be involved in the proliferation and functional differentiation of zona reticularis.

Are estrogens locally produced in postnatal human adrenal cortex?

Belgorosky found that ARO protein was expressed in the adrenal medulla of the 3 Grs and in subcapsular ZG of Gr 3.

Is aromatase expressed in chromaffin in human adrenal medulla?

ARO protein was not expressed in adrenal medulla chromaffin cells of the post-adrenarche group which they studied.

Estradiol increased DHEA secretion and DHEA/Cortisol ratios under ACTH stimulation.

Despite her group’s efforts, the mechanism of post natal human adrenal zone formation remains undetermined. Several lines of evidence point to multiple factors including local adrenal maturational changes.