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

Res Exp Med (Berl). 1994;194(2):69-79. doi: 10.1007/BF02576368.


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.

MeSH terms

  • Adrenal Cortex / cytology
  • Adrenal Cortex / drug effects*
  • Adrenal Cortex / metabolism
  • Adrenal Cortex Hormones / analysis
  • Adrenal Cortex Hormones / metabolism*
  • Adrenal Medulla / drug effects*
  • Adrenal Medulla / metabolism
  • Animals
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Hypothalamo-Hypophyseal System / drug effects
  • Male
  • Neuropeptides / pharmacology*
  • Pituitary-Adrenal System / drug effects
  • Rats
  • Rats, Wistar


  • Adrenal Cortex Hormones
  • Neuropeptides
  • neuromedin U 8