The Interplay between Estrogen and Fetal Adrenal Cortex

Abstract

<jats:p>Estrogen is a steroid hormone that regulates embryogenesis, cell proliferation and differentiation, organogenesis, the timing of parturition, and fetal imprinting by carrying chemical messages from glands to cells within tissues or organs in the body. During development, placenta is the primary source of estrogen production but estrogen can only be produced if the fetus or the mother supplies dehydroepiandrosterone (DHEA), the estrogen prohormone. Studies show that the fetal zone of the fetal adrenal cortex supplies 60% of DHEA for placental estrogen production, and that placental estrogen in turn modulates the morphological and functional development of the fetal adrenal cortex. As such, in developed countries where humans are exposed daily to environmental estrogens, there is concern that the development of fetal adrenal cortex, and in turn, placental estrogen production may be disrupted. This paper discusses fetal adrenal gland development, how endogenous estrogen regulates the structure and function of the fetal adrenal cortex, and highlights the potential role that early life exposure to environmental estrogens may have on the development and endocrinology of the fetal adrenal cortex.</jats:p>

Diethylstilbestrol decreased adrenal cholesterol and corticosterone in rats

“…To explore the mechanism by which adrenal cholesterol is reduced, further study of serum lipoproteins and cholesterol using short-term DES administration is required. Adrenal steroids play important roles not only in foetal and neonatal growth and development but also in labour and childbirth (Chida et al 2011, Kaludjerovic & Ward 2012. Therefore, chronic corticosterone suppression induced by DES has the potential to disrupt the regulators of endocrine homeostasis and to facilitate the impairment of stress resistance.…”

“…Although the detailed mechanism of DES action and its pharmacokinetics are not well understood, DES has been shown to bind to the ERs (Korach & McLachlan 1985, Kuiper et al 1997, Henley & Korach 2006. While DES is no longer used clinically for the prevention of miscarriage, it remains a useful compound for investigating the mechanism of action of exogenous oestrogens (Kaludjerovic & Ward 2012). DES has been extensively used as a treatment for prostate cancer in humans.…”

“…It is important to identify the initial targets and the early adverse effects of DES by following reproductive abnormalities in adult males. Results of the DES studies are currently being used to better characterise the biological effects of other oestrogenic compounds (Kaludjerovic & Ward 2012). Owing to the complexity of the processes involving DES, it is difficult to determine the molecular mechanism until a specific toxic effect is observed.…”

“…Owing to the complexity of the processes involving DES, it is difficult to determine the molecular mechanism until a specific toxic effect is observed. As described in Kaludjerovic & Ward (2012), it would be valuable to elucidate the mechanism and to identify the multiple pathways involved in DES toxicity. The triggers that elicit the aforementioned toxic effects have yet to be identified.…”

Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats

“…Fetal adrenal cortex development is dependent on placental estrogen and the existence of both types of estrogen receptors in the fetal gland (Kaludjerovic & Ward 2012) allows for a genomic action of BPA during developmental exposures. Additional nongenomic or epigenetic BPA actions in the adrenals, already reported for other tissues (Zsarnovszky et al 2005, Doshi et al 2011, cannot be excluded.…”