Regulatory effects of 5 beta-reduced steroids.
The first section of this publication summarizes early work according to which 5 beta-pregnanedione is an important metabolite of progesterone in the early stages of the chick embryo's adrenal steroidogenesis, then decreasing gradually as corticosteroidogenesis increases. In the second section a model is described in which adrenal 3 beta-ol hydroxylase-isomerase of the 17-day-old chicken is suppressed pharmacologically, this suppression being correlated with that of the synthesis of aminoevulinic acid (ALA), the first and rate-limiting step of the heme pathway. 5 beta-Pregnanedione (10(-7)-10(-6) M) restored ALA synthesis in this inhibited model to normal values. The effect of 5 beta-pregnanedione was specific since other steroids tested: progesterone; 5 alpha-pregnanedione; corticosterone or estradiol, did not stimulate ALA. Since heme formation by steroidogenic glands contributes to the synthesis of cytochrome P450 rather than hemoglobin, 5 beta-pregnanedione was also assayed as a stimulator of this enzyme system and was found to increase cytochrome P450 in adrenals and testes but not in the liver. In view of these results a hypothesis is advanced according to which 5 beta-reduced progestagens and androgens stimulate cytochrome P450 formation, i.e. the synthesis of progesterone and higher hydroxylated steroids, by steroidogenic glands in the event of an excessive precursor reduction.
Aragonés
A
A
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Gonzalez
C B
CB
Spinedi
N C
NC
Lantos
C P
CP
D000622:Aminolevulinic Acid / Q000378:metabolism; D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D003345:Corticosterone / Q000378:metabolism / Q000502:physiology; D003489:Cyanoketone / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000502:physiology; D008297:Male; D010084:Oxidation-Reduction; D011277:Pregnanediones / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism / Q000502:physiology; D013148:Spironolactone / Q000494:pharmacology; D013256:Steroids / Q000378:metabolism / Q000502:physiology*
D011277:Pregnanediones; D013256:Steroids; D013148:Spironolactone; D003489:Cyanoketone; D011374:Progesterone; D004958:Estradiol; D000622:Aminolevulinic Acid; D003577:Cytochrome P-450 Enzyme System; D003345:Corticosterone