Effect of Androgen on Adrenal Steroidogenesis in Normal Women*

Abstract

Ovarian hyperandrogenism may induce adrenal enzymatic defects that mimic true inherited disorders of adrenal hormone biosynthesis. To assess the effect of hyperandrogenism on adrenal steroidogenesis, seven normal ovulatory women were studied on 2 days during the early follicular phase of their cycles. Plasma 17-hydroxyprogesterone (17-Prog), 17-hydroxypregnenolone, dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione (Adione), testosterone (T), 11-deoxycortisol, and cortisol concentrations were measured every 15 min for 3 h after iv injection of 0.25 mg ACTH (day 1) and pretreatment with dexamethasone on each day. On the second study day, T (80 micrograms/h) was infused iv for 5 h, and ACTH was given after 2 h of T infusion. The T infusion raised mean serum T levels from 1.2 +/- 0.3 (+/- SE) to 8.6 +/- 0.6 nmol/L. The maximum incremental (delta max) plasma Adione response to ACTH was significantly higher (2.6 +/- 0.3 to 3.2 +/- 0.4 nmol/L; P less than 0.009) during the T infusion, while the delta max responses of the other steroids did not change. There was an increase in the delta max 17-Prog to cortisol ratio (4.9 +/- 0.7 to 7.0 +/- 1.0; P less than 0.05), but no change in the delta max 17-Prog to Adione or 17-hydroxypregnenolone to DHEA ratios and no changes in the delta max delta 5- to delta 4-steroid ratios. These data suggest that acute T elevations result in subtle inhibition of 21-and/or 11 beta-hydroxylase activities, but not in 17-20-desmolase or 3 beta-ol activities.

Intra-adrenal factors are not involved in the differential control of cortisol and adrenal androgens in human adrenals

“…However, the mechanism by which testosterone may affect adrenal steroidogenesis has not been defined previously. Oestrogens have been shown to inhibit DHEA production (30), and evidence from clinical studies suggests that androgens may inhibit 11b-hydroxylase and 21-hydroxylase enzyme activity (19,31). Our data that suggest a direct correlation of age with increasing androstenedione/ DHEA ratios are consistent with increasing conversion of DHEA to androstenedione with age in adrenals from males younger than 30 years, as a result of increased 3b-hydroxysteroid-dehydrogenase, D 4-5 isomerase enzyme system activity.…”

“…Parker et al (22) also reported stimulatory effects of joining peptide on adrenal androgen production, but others have not confirmed this (24,25). Evidence also exists that gonadal steroids influence adrenal glucocorticoid and androgen secretion: for example, testosterone increases the adrenal response to ACTH stimulation (19,20). A 60 000 molecular weight glycoprotein isolated from human pituitary has been reported to stimulate DHEA but not cortisol secretion (28), and another study has shown that a peptide other than ACTH from human fetal pituitary stimulated DHEAS but not cortisol, in fetal adrenal cells (29).…”

“…The potential endogenous adrenal gland mechanisms regulating adrenal androgen secretion include maturation and zonation of the adrenal gland (11), adrenal blood flow that may expose the inner zone to high concentrations of cortisol (12), and changes in the properties of the adrenal enzymes and their co-factors (13)(14)(15). Alternatively, factors outside the adrenal gland have been proposed, such as prolactin (16), growth hormone (17), insulin (18), sex steroids (19,20) and fragments of the ACTH precursor molecule, pro-opiomelanocortin, such as b-endorphin (21) and joining peptide (21,22). The existence of such a cortical androgen stimulating hormone has been disputed (23)(24)(25).…”

Adrenal 21-hydroxylase gene mutations in Slovenian hyperandrogenic women: evaluation of corticotrophin stimulation and HLA polymorphisms in screening for carrier status

“…Falsely positive ACTH tests may be due to high 17-OHP concentrations reflecting adrenal and non-adrenal secretion of this steroid precursor (30). Also, other adrenal and ovarian androgens may interfere with adrenal steroidogenesis, mimicking steroid profiles of patients with 21-hydroxylase deficiency (36). Finally, high 17-OHP concentrations may be the consequence of generalised hyperreactivity of the adrenal cortex in hyperandrogenic women (30).…”

Adrenal Disorders and Polycystic Ovary Syndrome

“…One hypothesis is that the ele vated gonadal steroid levels (androgens or oestrogens) modify the function of the adrenal enzymes [1,13]. Sup port for this hypothesis comes from studies of the effects of acute androgen infusions in normal women [13], ACTH stimulation was performed basally and during the infusion of testosterone (resulting in supraphysiologic tes tosterone levels) for at least 3 h. There were significant increases after ACTH administration during testosterone infusion in the ratio of 17-hydroxyprogesterone (170HP) to cortisol, suggesting decreased activity of either 21OHD or 11 OHD. These findings suggest that testosterone can alter the function of these enzymes.…”