beta-Lipotropin-stimulated adrenal steroid production.
The present study was undertaken to examine the mechanism whereby beta-lipotropin stimulates adrenal steroidogenesis. In guinea pig adrenal cells, beta-lipotropin (10(-8) M) increased basal steroid production 6-, 4-, and 5-fold for cortisol, androstenedione, and dehydroepiandrosterone (DHEA), respectively, whereas the corresponding responses to adrenocorticotropin (ACTH) (10(-9) M) were 12-, 8-, and 7-fold. The conversion of cholesterol to pregnenolone was studied in cells treated with trilostane, an inhibitor of 3 beta-hydroxysteroid delta 4-5 isomerase. beta-Lipotropin (10(-10) and 10(-8) M) and ACTH (10(-9) M) stimulated pregnenolone production in trilostane-treated cells. The production of cortisol and androgens from precursor steroids was also studied in cells treated with aminoglutethimide, an inhibitor of cholesterol side chain cleavage, after addition of exogenous pregnenolone, 17-hydroxypregnenolone, progesterone, or DHEA. Neither ACTH nor beta-lipotropin stimulated cortisol, androstenedione, or DHEA production in the presence of exogenous precursors in aminoglutethimide-treated cells. No inhibition of the beta-lipotropin- or ACTH-stimulated cortisol or androstenedione responses was demonstrated with the opioid receptor antagonist naloxone (10(-11) to 10(-5) M). The results suggest that beta-lipotropin stimulates steroidogenesis by acting on the conversion of cholesterol to pregnenolone and that its effects are not mediated via an opioid receptor but may be mediated via an ACTH receptor.
O'Connell
Y
Y
Department of Endocrinology, St. Vincent's Hospital, Dublin, Ireland.
McKenna
T J
TJ
Cunningham
S K
SK
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000728:Androgens / Q000096:biosynthesis; D000818:Animals; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000096:biosynthesis; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D013256:Steroids / Q000096:biosynthesis*; D013268:Stimulation, Chemical; D008083:beta-Lipotropin / Q000494:pharmacology*
D000305:Adrenal Cortex Hormones; D000728:Androgens; D009292:Narcotic Antagonists; D013256:Steroids; D009270:Naloxone; D000324:Adrenocorticotropic Hormone; D008083:beta-Lipotropin; D006854:Hydrocortisone