Effect of thyroidectomy on the rat adrenal cortex enzyme activities involved in corticosterone and aldosterone biosynthesis.
The effect of thyroidectomy on corticosterone and aldosterone biosynthesis, in rat adrenal cortex, were investigated in vitro. Thyroidectomy slowed down by about 30% the activity of microsomal 21 hydroxylase and mitochondrial 11 beta hydroxylase, the two stages leading to corticosterone formation from progesterone. The plasma corticosterone concentration also diminished in thyroidectomized rat. The mitochondrial enzyme system catalyzing the conversion of corticosterone into aldosterone included both 18 hydroxylase and 180H dehydrogenase. In the absence of thyroid hormone, values of both enzyme activity slowed down by about 30%. Thus thyroidectomy induced a general decrease in all mitochondrial hydroxylation processes requiring NNADPH as energetic cofactor. Mitochondrial NADPH was mainly synthesized by the activity of NADP+ malic enzyme and pyridine nucleotide transhydrogenase; the activity of both enzymes was determined in submitochondrial particles from adrenal cortex of normal and thyroidectomized rats. The activity of NADP+ malic enzyme and non energy-dependent transhydrogenase in the direction of NADPH formation dropped significantly after thyroidectomy, thus reducing the amount of NADPH available for hydroxylating mechanisms. The results should be compared to the large rise in th cytosolic malic enzyme level caused by thyroidectomy. The latter also ensured that the transhydrogenase reaction did not vary in the direction of NADP+ formation. Further, the drop in NADPH synthesis after thyroidectomy was coupled with a decrease in phosphorylation rate of added ADPH by adrenal cortex mitochondria of thyroidectomized rat. These findings might account for the general decline in the energy-dependent processes involved in steroidogenesis, a decline mainly due to the lowering of the H+ ions gradient driving ATP and NADPH synthesis through electron transfer.
D000302:Adrenal Cortex / Q000201:enzymology*; D000450:Aldosterone / Q000096:biosynthesis*; D000818:Animals; D003345:Corticosterone / Q000096:biosynthesis*; D019405:Cytochrome P-450 CYP11B2; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology; D009249:NADP / Q000096:biosynthesis; D009250:NADP Transhydrogenases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism; D013255:Steroid 21-Hydroxylase / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism; D013965:Thyroidectomy
D000450:Aldosterone; D009249:NADP; D006913:Hydroxysteroid Dehydrogenases; C029791:18-hydroxycorticosterone dehydrogenase; D008291:Malate Dehydrogenase; D013250:Steroid Hydroxylases; D013255:Steroid 21-Hydroxylase; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D009250:NADP Transhydrogenases; D003345:Corticosterone