The steroidogenic effects of beta-endorphin and joining peptide: a potential role in the modulation of adrenal androgen production.
This study examines the androgen-stimulating properties of pro-opiomelanocortin-derived peptides, ACTH, beta-endorphin (beta-End) and joining peptide (JP). Ten different cell suspensions were prepared from ten human adrenal glands. ACTH and JP stimulated cortisol, androstenedione (delta 4) and dehydroepiandrosterone (DHEA) production (P < 0.05); beta-End stimulated only delta 4 and DHEA production. beta-End brought about significant increases in the delta 4 or DHEA to cortisol ratios. The addition of beta-End (10(-10) M) suppressed ACTH-stimulated cortisol production from 7573 +/- 2960 to 5994 +/- 2654 pmol/10(6) cells (means +/- S.E.M.; P < 0.05). The addition of beta-End did not affect ACTH-stimulated delta 4 production (210 +/- 88 and 236 +/- 105 pmol/10(6) cells). JP (10(-10) M) inhibited ACTH-stimulated cortisol production so that the mean values fell to 5186 +/- 2588 and also inhibited DHEA production, from 240 +/- 48 to 180 +/- 33 pmol/10(6) cells. These results suggest that the relative production of androgen to cortisol is greater in response to beta-End and JP than in response to ACTH. If blood levels of these peptides rise to herald adrenarche as reported for beta-End, suppression of cortisol production may result in an increase in ACTH to correct cortisol levels resulting in an increase in delta 4 and DHEA levels. This may explain the occurrence of increasing androgen levels at adrenarche.
Clarke
D
D
Department of Endocrinology, St Vincent's Hospital, Dublin, Ireland.
Fearon
U
U
Cunningham
S K
SK
McKenna
T J
TJ
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000728:Androgens / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000494:pharmacology*; D013268:Stimulation, Chemical; D001615:beta-Endorphin / Q000494:pharmacology*
D000728:Androgens; D010446:Peptide Fragments; D010455:Peptides; C078895:joining peptide, pro-opiomelanocortin; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone