Induction of plasma proangiotensin by steroid hormones in nephrectomized rats.
The response of plasma proangiotensin to various steroids was studied in bilaterally nephrectomized rats. In male animals, estradiol and testosterone increased the proangiotensin level up to 250% and 180% respectively. In female animals, both hormones lead to an increase of proangiotensin up to 220% of the controls, when given at optimal dose. The dose dependence on estradiol and testosterone was about the same in male rats, whereas in female animals the formation of proangiotensin was stimulated by much lower doses of estradiol as compared to testosterone. Adrenalectomy plus nephrectomy reduced the proangiotensin level to 20-30% of the value measured in animals nephrectomized only. Cortisol caused a rapid increase of plasma proangiotensin up to 1000% in adrenalectomized animals. Independent from the adrenal state, the amounts of cortisol necessary to induce proangiotensin were very low as compared to the dose response of other proteins, biosynthesis of which is regulated by cortisol. 21-Dehydrocortisol and aldosterone induced proangiotensin with the same efficiency as cortisol, whereas several other chemically related steroids were less active or inactive. Comparing the biological activity of the various steroids tested, it has to be concluded that the delta 4-ene-3-one structure of ring A, the 11 beta-OH group of ring C and the carbonyl group at C-20 of the ketol side-chain of cortisol are very important with respect to proangiotensin induction. The response of proangiotensin to cortisol, 21-dehydrocortisol and aldosterone could be inhibited by actinomocin D and cycloheximide, whereas the effects of estradiol and testosterone could be reversed by cycloheximide only.
D000315:Adrenalectomy; D000808:Angiotensinogen / Q000097:blood*; D000809:Angiotensins / Q000097:blood*; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009392:Nephrectomy; D051381:Rats; D012737:Sex Factors; D013739:Testosterone / Q000494:pharmacology*
D000809:Angiotensins; D000808:Angiotensinogen; D003609:Dactinomycin; D013739:Testosterone; D004958:Estradiol; D003513:Cycloheximide; D006854:Hydrocortisone