Phytoestrogens Alter Adrenocortical Function: Genistein and Daidzein Suppress Glucocorticoid and Stimulate Androgen Production by Cultured Adrenal Cortical Cells¹

Abstract

Phytoestrogens influence a variety of biological processes. As 17beta-estradiol alters adrenocortical cell function, we examined whether the dietary phytoestrogens, genistein and daidzein, have related effects. In cultured human fetal and postnatal adrenal cortical cells, genistein and daidzein (both 0.4-40 micromol/L) decreased ACTH-stimulated cortisol production to basal levels (ED50, 1-4 micromol/L). In the adult adrenocortical cell line, H295, genistein, daidzein, and 17beta-estradiol (10 micromol/L) decreased cAMP-stimulated cortisol synthesis in a similar fashion. Neither genistein nor daidzein altered basal or ACTH-stimulated dehydroepiandosterone sulfate (DHEA-S) production in fetal adrenocortical cells, whereas in postnatal adrenocortical cells, DHEA and DHEA-S were markedly increased (ED50, 1-4 micromol/L). In H295 cells, basal and cAMP-stimulated DHEA production were similarly increased by the phytoestrogens and 17beta-estradiol. Genistein and daidzein did not affect the expression of steroid-metabolizing enzymes. However, genistein and daidzein specifically inhibited the activity of 21-hydroxylase (P450c21); the activities of other steroidogenic enzymes were not affected. Thus, phytoestrogens may decrease cortisol synthesis by suppressing the activity of P450c21 and, as a consequence, increase DHEA/DHEA-S synthesis by shunting metabolites away from the glucocorticoid synthetic pathway. Therefore, consumption of foods containing phytoestrogens may alter adrenocortical function by decreasing cortisol and increasing androgen production.

Neither soyfoods nor isoflavones warrant classification as endocrine disruptors: a technical review of the observational and clinical data

“…In theory, isoflavones may influence estrogen action by virtue of effects on enzymes involved in steroid metabolism, such as aromatase (Rice, Mason, and Whitehead 2006), 17bhydroxysteroid dehydrogenases, steroid sulfatases and sulfotransferases (Lacey et al 2005), among others (Mesiano et al 1999;Ohno et al 2002). Isoflavones could also affect biologically active levels of hormones by affecting SHBG concentrations (Loukovaara et al 1995).…”

Isoflavones Alter Hypothalamic–Pituitary–Adrenal Axis Response Following Photoperiod Alteration

“…However, the literature regarding the effects of isoflavones on HPA axis reactivity and behavior is less clear. Most studies in animals have found that isoflavonesare beneficial leading to anxiolytic effects on behavior and HPA axis reactivity, based on their increased affinity for ERβ (Mesiano et al, 1999;Lephart et al, 2002;Lephart et al, 2003). However, other studies have found varying results including anxiogenic or no effect on behavior (Hartley et al, 2003;Bu et al, 2005).…”

“…Past studies looking at the effects of isoflavones on HPA axis reactivity have shown increases and decreases, as well as no effect on CORT secretion (Mesiano et al, 1999;Hartley et al, 2003;Lephart et al, 2003;Lephart et al, 2004;Bu et al, 2005). Furthermore, the presence of isoflavones in an animal's diet have been shown to modulate behavioral outcome, producing both anxiolytic and anxiogenic type of effects on behavior (Lephart et al, 2002;Hartley et al, 2003;.…”

“…Isoflavones are a type of phytoestrogen, which are naturally occurring compounds found in plants, that serve as a main source of protein in many soy products and standard rodent chows (Mullner, 2000;Lund and Lephart, 2001;Lephart et al, 2004;Wu et al, 2004;Patisaul and Jefferson, 2010). They have been shown to elicit estrogenic and anti-estrogenic effects through their interaction with both estrogen receptors (ERα and ERβ) due to their structural similarity to 17β estradiol (Mesiano et al, 1999;Morito et al, 2001;Miyazaki, 2004;Bedell et al, 2014). These neuroendocrine disruptors have been shown to have varying effects on the functioning of the hypothalamic-pituitary-adrenal (HPA)axis, which is known to mediate the physiological response to stressors, both physical and psychogenic (Handa and Weiser, 2014;Myers et al, 2014).…”

Genistein: A focus on several neurodegenerative diseases

“…Cortisol is a steroidal hormone that increases blood sugar levels through improving carbohydrate, fat, and protein metabolism as well as gluconeogenesis. In adrenocortical cell lines, genistein treatment suppressed the cAMP-stimulated cortisol synthesis (Mesiano et al, 1999). Moreover, genistein is involved in the modulation of cellular and humoral immunity at multiple levels, such as the inhibition of the activation of NFκB and the reduction of inflammatory cytokine levels (Jonas et al, 1995), which indicate that genistein has anti-inflammatory functions.…”