DHEA - A precursor of ERβ ligands

What is DHEA and why is there so much public interest in this steroid which has been touted as the fountain of youth and is supposed to have all kinds of health benefits? Endocrinologists have been fascinated with DHEA for a long time because of its high production in the fetal adrenals and its continued high levels until the 7th decade of life. Yet there is still little agreement about its physiological functions. In its simplest terms endocrinology is the communication between at least three organs: one sends a message, one releases a hormone into the blood in response to the message and one responds to the hormone. DHEA is produced by a specific zone of the adrenal cortex, the zona reticularis, whose sole function is to produce this steroid. Glucocorticoids and mineralocorticoids which are C21 steroids are produced in two other zones of the adrenal cortex called the zona fasicularis and the zona glomerulosa, respectively. Being C21 steroids, they cannot be synthesized from DHEA which is a C19 steroid. To date there is no known hormone which specifically stimulates the zona reticularis and there is no known specific receptor for DHEA. Thus DHEA does not qualify as a hormone. DHEA could have autocrine or paracrine effects but, so far, there is no known effect of DHEA on either the cells of the zona glomerulosa or the zona fasicularis. Of course DHEA could have functions as a local precursor of androgens or estrogens and many studies have reported on the beneficial effects of transdermal or transvaginal administration of DHEA in postmenopausal women. This review will consider two of the potential functions of DHEA as a precursor of estrogen receptor beta (ERβ) ligands.