Atrial and brain natriuretic peptide in adrenal steroidogenesis.
We elucidated the role of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in human and bovine adrenocortical steroidogenesis. The urinary volume, sodium excretion and cyclic GMP (cGMP) excretion and plasma cGMP were markedly increased by the synthetic alpha-human ANP (alpha-hANP) infusion in healthy volunteers. Plasma arginine vasopressin (AVP) and aldosterone levels were significantly suppressed. Both ANP and BNP inhibited aldosterone, 19-OH-androstenedione, cortisol and DHEA secretion dose-dependently and increased the accumulation of intracellular cGMP in cultured human and bovine adrenal cells. alpha-hANP significantly suppressed P450scc-mRNA in cultured bovine adrenal cells stimulated by ACTH. Autoradiography and affinity labeling of [125I]hANP, and Scatchard plot demonstrated a specific ANP receptor in bovine and human adrenal glands. Purified ANP receptor from bovine adrenal glands identified two distinct types of ANP receptors, one is biologically active, the other is silent. A specific BNP receptor was also identified on the human and bovine adrenocortical cell membranes. The binding sites were displaced by unlabelled ANP as well as BNP. BNP showed an effect possibly via a receptor which may be shared with ANP. The mean basal plasma alpha-hANP level was 25 +/- 5 pg/ml in young men. We confirmed the presence of ANP and BNP in bovine and porcine adrenal medulla. Plasma or medullary ANP or BNP may directly modulate the adrenocortical steroidogenesis. We demonstrated that the lack of inhibitory effect of alpha-hANP on cultured aldosterone-producing adenoma (APA) cells was due to the decrease of ANP-specific receptor, which caused the loss of suppression of aldosterone and an increase in intracellular cGMP.
Nawata
H
H
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Ohashi
M
M
Haji
M
M
Takayanagi
R
R
Higuchi
K
K
Fujio
N
N
Hashiguchi
T
T
Ogo
A
A
Nakao
R
R
Ohnaka
K
K
D000302:Adrenal Cortex / Q000378:metabolism*; D000345:Affinity Labels; D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000502:physiology*; D001345:Autoradiography; D002417:Cattle; D006152:Cyclic GMP / Q000096:biosynthesis / Q000652:urine; D006801:Humans; D008969:Molecular Sequence Data; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D011863:Radioimmunoassay; D013256:Steroids / Q000096:biosynthesis*
D000345:Affinity Labels; D009419:Nerve Tissue Proteins; D013256:Steroids; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP