Hypertension caused by prenatal testosterone excess in female sheep.
Polycystic ovary syndrome (PCOS), a leading cause of infertility, affects approximately 10% of women of reproductive age. The etiology and pathophysiology of PCOS are poorly understood. PCOS is multifaceted and includes reproductive abnormalities and components of the metabolic syndrome such as insulin resistance, obesity, dyslipidemia, and hypertension. Exposure to excess testosterone (T) during the prenatal period may predispose individuals to PCOS phenotype. The goal of this study was to determine whether hypertension and dyslipidemia occur in a well-characterized model of PCOS produced by prenatal treatment of sheep with T. Radiotelemetry was used to measure blood pressure over a 24-h period in conscious, undisturbed animals. To normalize circulating estradiol levels across treatment, control (n = 4) and prenatal T-treated (100 mg T propionate im twice weekly from days 30 to 90 of fetal life, n = 4) 2-yr-old females were ovariectomized, instrumented with a radiotelemetry transmitter, and clamped with early follicular phase levels of estrogen using an implant. Six days later, a 24-h recording period commenced. Prenatal T-treated sheep were hypertensive compared with control sheep, and heart rate tended to be higher. T-treated sheep had hyperglycemia, insulin resistance, hypernatremia, and hyperchloremia, and both total and LDL cholesterol tended to be higher. Plasma aldosterone and epinephrine were significantly lower in T-treated sheep, whereas norepinephrine was unchanged. This first-ever use of radiotelemetric blood pressure recordings in sheep demonstrates that mild hypertension, a risk factor reported in some women with PCOS, is also a feature of the sheep model of PCOS produced by prenatal T treatment.
King
Andrew J
AJ
Deparetment of Pharmacology and Toxicology, B440 Life Sciences, Michigan State University, East Lansing, MI 48824, USA. kingand@msu.edu
Olivier
N Bari
NB
Mohankumar
P S
PS
Lee
James S
JS
Padmanabhan
Vasantha
V
Fink
Gregory D
GD
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002712:Chlorides / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000139:chemically induced*; D004837:Epinephrine / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006943:Hyperglycemia / Q000175:diagnosis; D006955:Hypernatremia / Q000139:chemically induced; D006973:Hypertension / Q000139:chemically induced*; D007333:Insulin Resistance; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012756:Sheep; D043343:Testosterone Propionate / Q000008:administration & dosage* / Q000494:pharmacology
D002712:Chlorides; D000450:Aldosterone; D002784:Cholesterol; D043343:Testosterone Propionate; D004837:Epinephrine