Urinary free and serum 19-nor-deoxycorticosterone in adrenal regeneration hypertension.

Abstract

SUMMARY Adrenal regeneration hypertension (ARH) is caused by increased secretion of mineralocorticoids. Deoxycorticosterone (DOC), which has been found in increased concentrations in the blood of rats with ARH after the second week, must play an important role in the pathogenesis of ARH. However, the increased sodium reabsorption early in the regeneration suggests that another steroid might also play a role in ARH. We previously isolated 19-nor-deoxycorticosterone (19-nor-DOC), a mineralocorticoid with two to five times the potency of DOC, from the urine of rats with regenerating adrenals. In this study, ARH was produced, and the urinary excretions of free DOC and 19-nor-DOC and serum 19-nor-DOC were measured on the 23rd day of regeneration, when the systolic blood pressure of the ARH rats was 172 ± 5 mm Hg (SEM, n = 12) in comparison to 129 ± 4 mm Hg for the controls. Urine excretion of 19-nor-DOC was increased from 0.9 ± 0 . 1 ng/day in controls to 2.3 ± 0.6 ng/day in ARH for DOC and from 5.0 ± 1.1 ng/day in controls to 7.9 ± 1.4 ng/ day in ARH for 19-nor-DOC. Serum 19-nor-DOC was undetectable in both groups. These studies suggest that increased DOC might play an important role in ARH by serving as the initial substrate for the formation of a more powerful mineralocorticoid, 19-nor-DOC, as well as by its own mineralocorticoid activity. However, for 19-nor-DOC to be important it would have to be formed from a precursor at the target organ, since it does not seem to be a circulating steroid. scribed by Skelton, 1 is believed to be due to excessive secretion of a mineralocorticoid that occurs as a consequence of adrenal disruption and subsequent regeneration. Most known mineralocorticoids have been measured and found to be either normal or below normal.2 One exception is DOC, which investigators have described as elevated in the plasma, • w even though DOC production is low in the adrenal incubates from ARH animals at the same stage. 4 6 The acceptance that DOC is the sole causative factor for ARH has not been uniform. Hall and Hall 7 have proposed that the inconsistent finding of saline poly-, dipsia argues against DOC being the cause of ARH. In addition, during the first week of ARH when DOC production and plasma concentrations are low, 3 there is evidence of a salt-retaining factor of adrenal origin 8 ' 9 of unknown identity. hypertension • mineralocorticoidsWe have identified a powerful mineralocorticoid, 19-nor-deoxycorticosterone (19-nor-DOC), in the urine of rats with ARH 10 and have recently developed a method to measure the urinary excretion of 19-nor-DOC in rats. We are reporting our results of the measurements of free 19-nor-DOC and DOC in the urine and 19-nor-DOC in the serum of rats with adrenal regeneration hypertension.

Endogenous corticosteroid biosynthesis in subjects after bilateral adrenalectomy

“…There is evidence of adrenal regrowth in salt‐fed adrenalectomized rats that can develop ‘adrenal regeneration hypertension’ with evidence of mineralocorticoid excess 27 . However, in this poorly understood model, bilateral adrenalectomy was incomplete, with enucleation of the left adrenal gland (leaving an intact capsule and zona glomerulosa) 28 . The presence of adrenal tissue in humans after bilateral adrenalectomy has not been studied in detail and would require precise functional imaging.…”

“…27 However, in this poorly understood model, bilateral adrenalectomy was incomplete, with enucleation of the left adrenal gland (leaving an intact capsule and zona glomerulosa). 28 The presence of adrenal tissue in humans after bilateral adrenalectomy has not been studied in detail and would require precise functional imaging. Brauckhoff et al described a case series of 10 subjects who underwent subtotal bilateral adrenalectomy, leaving 15-30% of the cortex intact.…”

Functional expression of the cDNAs encoding rat 11β‐hydroxylase [cytochrome P450(11β)] and aldosterone synthase [cytochrome P450(11β, aldo)]

“…However, neither product was found in the culture medium of the pSVP450(1 lp, a1do)-transfected cells. At present, the physiological roles of these 19-hydroxylated or 19-oxidized steroids remain to be established, although some interesting observations have been reported in the case of rat adrenal regeneration hypertension [22,23] and spontaneous hypertension [24].…”