Effects of neuromedin U-8 on the secretory activity of the rat adrenal cortex: evidence for an indirect action requiring the presence of the zona medullaris.
The acute effect of increasing concentrations (from 10(-8) to 10(-6) M) of neuromedin U-8 (NMU-8) on steroid secretion of rat adrenal gland was investigated in vitro by high-pressure liquid chromatography. The production of the following steroids was measured: pregnenolone (PREG), progesterone (PROG), 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18OH-DOC), 18-hydroxycorticosterone (18OH-B) and aldosterone (ALDO). NMU-8 had no effects on either dispersed adrenocortical cells or fragments of adrenocortical autotransplants lacking medullary chromaffin cells. Conversely, NMU-8 exerted concentration-dependent secretagogue effects on adrenal slices, including both cortex and medulla. At all concentrations tested, NMU-8 increased the production of both PREG and total post-PREG steroids. The increase in total post-PREG steroid output induced by low concentrations of NMU-8 (10(-8) M) was due to similar rises in the production of non-18-hydroxylated steroids (PROG, DOC and B) and 18-hydroxylated hormones (18OH-DOC, 18OH-B and ALDO); conversely, that provoked by higher concentrations of the neuropeptide (10(-7) to 10(-6) M) was almost exclusively caused by the rise in the yield of 18-hydroxylated steroids. The stimulating effect of NMU-8 on PREG output was blocked by both alpha-helical-CRH and corticotropin-inhibiting peptide, which are competitive inhibitors of CRH and ACTH, respectively. The following conclusions have been drawn: (1) NMU-8 affects adrenal steroid secretion indirectly by acting on the medullary chromaffin cells, which in turn may paracrinally stimulate the cortical ones; (2) at all concentrations tested, NMU-8, by stimulating the intramedullary CRH/ACTH system, causes a net rise in the activity of the early rate-limiting step of steroidogenesis, with the consequent increase in the output of the entire spectrum of post-PREG steroids; and (3) at higher concentrations (over 10(-8) M), NMU-8 also elicits the release from chromaffin cells of a factor (not yet known) that specifically enhances 18-hydroxylase activity.
Malendowicz
L K
LK
Department of Histology and Embryology, School of Medicine, Poznan, Poland.
Andreis
P G
PG
Markowska
A
A
Nowak
M
M
Warchol
J B
JB
Neri
G
G
Nussdorfer
G G
GG
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000032:analysis / Q000378:metabolism*; D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000305:Adrenal Cortex Hormones; D009479:Neuropeptides; C046270:neuromedin U 8