19-Noraldosterone in pregnancy-induced hypertension.
Pregnancy-induced hypertension (PIH) is a frequent cause of maternal and neonatal morbidity and mortality. 19-Noraldosterone, which was shown to be synthesized in the human adrenal gland, exhibits potent mineralocorticoid and hypertensive activity. To examine the role of mineralocorticoids in the pathophysiology of PIH, we studied urinary 19-noraldosterone, tetrahydroaldosterone, free cortisol, and cortisone concentrations and mineralocorticoid receptor levels in peripheral blood mononuclear leukocytes, from 17 women with PIH and 16 normal pregnant women as controls. Sequence analysis of the mineralocorticoid receptor gene in PIH patients was also done. The 24-h urinary excretion of 19-noraldosterone was significantly lower in PIH (120 +/- 38 pmol/day) than in controls (358 +/- 55 pmol/day) (P < 0.05). Urinary tetrahydroaldosterone was also decreased in PIH compared with controls. Ratios of urinary free cortisol to cortisone (a measure of 11beta-hydroxysteroid dehydrogenase 2 activity) did not differ significantly between groups. Mineralocorticoid receptor density was significantly (P < 0.05) decreased in the PIH group (133 +/- 15 binding sites/cell) compared with controls (255 +/- 21 binding sites/cell). No mutations were found in the coding region of the mineralocorticoid receptor gene in PIH. These results suggest that circulating aldosterone, 19-noraldosterone, and renal 11beta-hydroxysteroid dehydrogenase2 do not contribute to the pathogenesis of PIH. Regulatory factors that cause the down-regulation of the mineralocorticoid receptor in PIH should be clarified.
Takeda
Yoshiyu
Y
Second Department of Internal Medicine, Kanazawa University, Japan. takeday@im2.m.kanazawa-u.ac.jp
Yoneda
Takashi
T
Demura
Masashi
M
Furukawa
Kenji
K
Usukura
Mikiya
M
Mabuchi
Hiroshi
H
D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000031:analogs & derivatives* / Q000097:blood* / Q000652:urine*; D005260:Female; D006801:Humans; D008901:Mineralocorticoids / Q000097:blood / Q000652:urine; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis / Q000652:urine*; D011247:Pregnancy; D018161:Receptors, Mineralocorticoid / Q000032:analysis / Q000235:genetics
D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; C027514:19-noraldosterone