title: Prenatal Testosterone Exposure Decreases Aldosterone Production but Maintains Normal Plasma Volume and Increases Blood Pressure in Adult Female Rats.
abstract: Plasma testosterone levels are elevated in pregnant women with preeclampsia and polycystic ovaries; their offspring are at increased risk for hypertension during adult life. We tested the hypothesis that prenatal testosterone exposure induces dysregulation of the renin-angiotensin-aldosterone system, which is known to play an important role in water and electrolyte balance and blood pressure regulation. Female rats (6 mo old) prenatally exposed to testosterone were examined for adrenal expression of steroidogenic genes, telemetric blood pressure, blood volume and Na(+) and K(+) levels, plasma aldosterone, angiotensin II and vasopressin levels, and vascular responses to angiotensin II and arg(8)-vasopressin. The levels of Cyp11b2 (aldosterone synthase), but not the other adrenal steroidogenic genes, were decreased in testosterone females. Accordingly, plasma aldosterone levels were lower in testosterone females. Plasma volume and serum and urine Na(+) and K(+) levels were not significantly different between control and testosterone females; however, prenatal testosterone exposure significantly increased plasma vasopressin and angiotensin II levels and arterial pressure in adult females. In testosterone females, mesenteric artery contractile responses to angiotensin II were significantly greater, while contractile responses to vasopressin were unaffected. Angiotensin II type-1 receptor expression was increased, while angiotensin II type-2 receptor was decreased in testosterone arteries. These results suggest that prenatal testosterone exposure downregulates adrenal Cyp11b2 expression, leading to decreased plasma aldosterone levels. Elevated angiotensin II and vasopressin levels along with enhanced vascular responsiveness to angiotensin II may serve as an underlying mechanism to maintain plasma volume and Na(+) and K(+) levels and mediate hypertension in adult testosterone females.
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, Texas.
authors.forename: Amar S
authors.initials: AS
authors.lastname: More
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, Texas.
authors.forename: Jay S
authors.initials: JS
authors.lastname: Mishra
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, Texas.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hankins
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, Texas kusathis@utmb.edu.
authors.forename: Sathish
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D019405:Cytochrome P-450 CYP11B2 / Q000378:metabolism; D005260:Female; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D010953:Plasma Volume / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D013739:Testosterone / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000804:Angiotensin II; D001127:Arginine Vasopressin; D013739:Testosterone; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2
keywords: AGTR1; aldosterone; angiotensin II; blood pressure; plasma volume; pregnancy; testosterone; vascular function; vasopressin